Histopathological and immunohistochemical studies on the elevation mechanism of cancer associated antigens, CEA and CA19-9, in gastric cancer patients

Correlation between CEA and CA19-9 levels of peripheral and draining venous blood, and 11 histopathologic and 2 immunohistochemical variables, was examined in 53 gastric cancer patients. CEA levels of draining blood were significantly higher than those of peripheral blood in 48 patients with CEA producing cancer. CA19-9 levels of draining blood were not different from those of peripheral blood in 33 patients with CA19-9 producing cancer. Elevation of CEA levels in the blood was most highly correlated with venous invasion, though the levels in draining blood were related to other 10 variables except tumor location and CEA distributed patterns of cancer lesions. These 10 variables relating to CEA elevation were highly associated with venous invasion. However, tumor location and CEA distributed patterns were not associated with venous invasion. While, elevation of CA19-9 levels in the blood was most highly correlated with lymphatic invasion and node metastasis, though the levels were related to the almost same variables which were highly associated with lymphatic invasion and node metastasis as CEA elevation-relating variables. These results suggest that CEA may be hematogenously drained by the portal system via the draining vein from the CEA producing cancer cells in the invasive veins, and that CA19-9 may be drained by the thoracic duct of lymphatic system.     

Carcinoembryonic antigen (CEA) levels of peripheral and portal blood and tumor histopathology in colorectal cancer

Correlation between CEA levels of peripheral and portal blood and 9 histopathologic variables were examined in 66 patients with colorectal cancer. CEA levels of portal blood (mean 26.6ng/ml and positive rate more than 5ng/ml, 59.1%) were significantly higher than those (8.1ng/ml and 33.3%) of peripheral blood. Elevation of CEA levels in portal and peripheral blood were most highly correlated with the grade of vein invasion and its location in the layer of colorectal wall, although the levels were related to the other 8 histopathologic variables such as tumor size, the grade of node metastases, Dukes stage and so on. CEA levels of portal blood elevated from 19.4ng/ml and 40% to 43.6ng/ml and 90.2% respectively following operative stimuli to cancer lesions with vein invasion, but the levels did not elevated in the lesions without its invasion. CEA levels of peripheral blood were as low as 5ng/ml in 3 out of 8 patients with liver metastases. However, the levels in portal blood were much higher than 5ng/ml in all the patients. These results suggested that CEA might be hematogenously drained by portal system from cancer cells in the invasive veins, but not by thoracic duct of lymphatic system, and also that the measurement of CEA in portal blood might be available to predict the vein invasion of cancer lesions and liver metastases in patients with colorectal cancer.     

Patients with high risk of hematogenous metastasis and recurrence in colorectal cancer: correlation with histopathologic variables and tumor markers, CEA and CA19-9, in peripheral and draining venous blood

Correlations of hematogenous metastasis with histopathologic variables, preoperative CEA and CA19-9 levels in peripheral (p) venous blood, and those in draining (d) venous blood were examined in 78 patients with colorectal cancer. Out of 10 histopathologic variables, location of venous invasion was most significantly correlated with hematogenous recurrence: the rate (11%) of v0 and/or sm-pm v(+) in 50 patients without the recurrence was significantly lower than that (89%) in 28 patients with the recurrence. On the other hand, the rate (68%) of ss-extra(+) in the latter was significantly higher than that (32%) of the former. The mean values (6 and 14 ng/ml) and positive rates (22 and 48%) greater than 5 ng/ml of p and d-CEA in 50 patients without the recurrence were significantly lower than those (14 and 189 ng/ml, 48 and 96%) in 28 patients with the recurrence. Patients with d-p CEA gradient greater than 5 ng/ml were found, respectively, in 34% of the former and 82% in the latter. The mean value (982 U/l) and positive rate (94%) greater than 37 U/ml of CA19-9 in peripheral blood of 28 patients with the recurrence were significantly higher than those (25 U/ml and 11%) of 50 patients without the recurrence. These results suggest that colorectal cancer patients with high risk of hematogenous metastasis and recurrence are the patients with ss-extra(+), the values of d-CEA, especially d-p CEA gradient, greater than 5 ng/ml and with p-CA19-9 value greater than 37 U/ml.     

Studies on the clinical evaluation of tissue polypeptide antigen (TPA) levels in the peripheral and draining venous blood of gastric cancer patients

Correlation with TPA levels of peripheral (p) and draining (d) venous blood, and 11 histopathologic variables, postoperative recurrence and survival was examined in 40 patients with gastric cancer. Elevation of d-TPA levels was correlated with tumor location, size, macroscopic type, invasive layer of gastric wall, venous invasion, node and liver metastases and stage classification, though elevation of p-TPA levels was correlated only with liver metastasis. No significant difference of p-TPA levels was found between the patients with and without cancer recurrence. d-TPA levels (mean 1318U/l and positive rate greater than 726U/l of mean +/- 2SD in patients with benign diseases, 59%) of the former were significantly higher than those (518U/l and 15%) of the latter. Correlation between d-TPA levels and recurrent sites was not found. Most of the patients with hematogenous recurrence showed the elevated p-TPA levels, but none of the patients with local recurrence revealed the elevation. Survival in both patients with non-elevated p- and d-TPA levels was significantly better than in patients with the elevated levels. These results suggest d-TPA levels are more closely correlated with histopathologic variables and postoperative recurrent rates than p-TPA levels, preoperative determination of p- and d-TPA levels is useful for the estimation of the postoperative prognosis and patients with elevated p- and d-TPA levels should be clinically treated as patients with high recurrence and poor prognosis.     

CEA levels of draining venous blood and draining-peripheral CEA gradient in colorectal cancer patients: correlation with postoperative survival

Correlation between preoperative CEA levels in draining venous blood (d CEA) and draining-peripheral (d-p) CEA gradient, and postoperative survival of 94 patients with colorectal cancer patients was examined. The positive rates of d CEA and d-p CEA gradient greater than 5 ng/ml (55.9% and 37.2%) in 59 alive patients were significantly (p less than 0.05) lower than those (77.1% and 57.1%) in 35 patients died of cancer recurrence within 4 years. Survival curve of the patients with positive d CEA and d-p CEA gradient were significantly (p less than 0.01) lower than those of the patients with negative d CEA and d-p CEA gradient. Survival curve of the patients with d-p CEA gradient greater than 10 ng/ml was significantly (p less than 0.001) lower than that of the gradient less than 10 ng/ml, and 4-year survival rates were 37.5% in the former patients and 68.3% in the latter patients. These results suggest that d CEA and d-p CEA gradient may be used as prognostic indicators of colorectal cancer patients. Clinically, the patients with positive d-p CEA gradient greater than 10 ng/ml are necessary to be treated as patients having very poor prognosis.     

Predictive factors for lymph node metastasis in early gastric cancer with submucosal invasion: analysis of a single institutional experience

OBJECTIVE: An accurate assessment of a potential lymph node metastasis is an important issue for the appropriate treatment of early gastric cancer. Minimizing the amount of invasive procedures used in cancer treatment is critical for improving the patient's quality of life. Therefore, this study analyzed the predictive risk factors for a lymph node metastasis in early gastric cancer with a submucosal invasion. METHODS: The data from 1043 patients surgically treated for early gastric cancer with submucosal invasion between 2002 and 2005 were reviewed retrospectively. The patients were divided into 3 layers according to their depth: SM1, SM2, and SM3. The clinicopathological variables predicting a lymph node metastasis were evaluated. RESULTS: A lymph node metastasis was observed in 19.4% of patients. The tumor size, histologic type, Lauren classification, tumor depth, and perineural invasion showed a positive correlation with the rate of lymph node metastasis and N category by univariate analysis. Multivariate analyses revealed the tumor size (>or=2 cm) and lymphatic involvement to be significantly and independently related to lymph node metastasis. The presence of lymphatic involvement was the strongest predictive factor for a lymph node metastasis, being observed in 43.8% of cases in which a lymph node metastasis had been revealed. No lymph node metastasis was observed in the 12 cases with no lymphatic involvement, SM1 invasion, and tumor size <1 cm. CONCLUSIONS: Lymphatic involvement and tumor size are independent risk factors for a lymph node metastasis in early gastric cancer with submucosal invasion. Minimal invasive treatment, such as endoscopic mucosal resection, may be possible in highly selective submucosal cancers with no lymphatic involvement, SM1 invasion, and tumor size <1 cm.     

Identification of carcinoembryonic antigen (CEA) in bile of patients with malignant biliary tract disease

As a diagnostant of malignant hepato-biliary tract disease, carcinoembryonic antigen (CEA) levels in the bile and serum were evaluated in 12 patients with benign and 19 patients with malignant hepato-biliary diseases. Of the 12 patients with benign disease, 3 had a residual choledocholithiasis. CEA levels were determined in 7 patients with cancer of the head of pancreas or of the duodenal ampulla. Bile samples were obtainedvia biliary tract drainage after allowing for sufficient time to exclude the effects of pre-existing bile stasis or inflammation. The average serum CEA levels from 8 patients with benign disease were 1.5±0.23 ng/ml in contrast to 3.3±0.55 ng/ml in 18 with a malignancy (p<0.05). The average CEA levels in bile from 9 patients with benign and 19 with a malignancy were 1.7±0.31 ng/ml and 7.6±1.70 ng/ml respectively (p<0.01). In 3 with residual choledocholithasis, serum and bile CEA levels were 2.0±0.46 ng/ml and 13.1±6.47 ng/ml. The serum and bile CEA levels from 7 patients with cancer of the head of the pancreas or of duodenal ampulla were 2.5±0.32 ng/ml and 8.8±3.3 ng/ml, respectively. Although measurement of both serum and bile CEA levels in patients with hepato-biliary tract disease proved to be useful for differentiation of malignant from benign disease, the high value obtained strongly suggests the presence of a malignancy in addition to the residual choledocholithiasis and cancer of the head of the pancreas or of the duodenal ampulla.     

甲状腺癌患者外周血CEACAM1水平及其临床意义

目的:探讨癌胚抗原黏附分子1(CEACAM1)在甲状腺癌患者外周血中水平及其对甲状腺癌的诊断价值。方法:用ELISA法检测76例甲状腺癌患者、48例甲状腺良性肿瘤患者和38例健康体检者外周血中CEACAM1水平,同时检测所有入组样本的癌胚抗原(CEA)及甲状腺球蛋白(TG)水平,分析外周血CEACAM1水平与甲状腺癌临床病理特征的关系,制作ROC曲线,比较CEACAM1、CEA、TG对甲状腺癌的诊断价值。结果:甲状腺癌患者血清CEACAM1水平明显高于甲状腺良性肿瘤患者及健康对照者(547.11 ng/mL vs.469.77 ng/mL、369.04 ng/mL,均P0.05)。血清CEACAM1水平与甲状腺癌的TNM分期和淋巴结转移有关(均P0.05)。血清CEACAM1水平诊断甲状腺癌的ROC曲线下面积为0.94,敏感性97.4%,特异性80.3%,CEACAM1对甲状腺癌的诊断价值优于CEA和TG。结论:血清CEACAM1检测对甲状腺癌的诊断及其病情评估有一定意义。     

胃黏膜下层癌淋巴结转移临床病理因素分析

【摘要】 目的 研究胃黏膜下层癌淋巴结转移率及其影响因素。 方法 回顾性分析南京医科大学第一附属医院1998年1月至2007年12月手术证实的181例胃黏膜下层癌的临床病理资料,对病人年龄、性别、肿瘤组织学类型、形态学类型、大小、部位、浸润深度、脉管内癌栓等与淋巴结转移的关系进行单因素与多因素分析。 结果 胃黏膜下层癌淋巴结转移率为20.44%。影响胃黏膜下层癌淋巴结转移的因素主要有肿瘤组织学类型（分化型 vs 分化不良型,P =0.0352）、直径大小（＜2cm vs ≥2cm,P =0.0143）、部位（近端胃vs胃体vs远端胃,P =0.0254）及脉管内癌栓（无vs有,P =0.0323）。Logistic回归分析显示肿瘤组织学类型与大小为胃黏膜下层癌淋巴结转移的独立性危险因素。结论 胃黏膜下层癌淋巴结转移与肿瘤组织学类型、大小、部位及脉管内癌栓等因素有关。临床上应参考上述临床病理因素判断淋巴结转移风险,制定合适的治疗方案。     

Immunosuppressive acidic protein (IAP) in gastric cancer patients

Immunosuppressive acidic protein (IAP) in the serum from peripheral, splenic and regional venous blood of gastric cancer patients was assayed. Peripheral venous blood was collected before, and for several months after the surgery. The IAP values of peripheral venous blood, increased with advancing cancer stage; in patients at the same cancer stage, the IAP values of venous blood draining from the cancer lesion were the highest. In curatively operated patients, the IAP values increased during the first postoperative month and decreased thereafter. In patients with non-resectable cancer and in patients subjected to palliative surgery, these values remained high; they increased sharply just before death. Determination of the serum IAP values in gastric cancer patients may be useful in estimating the immunological state of gastric cancer patients and for monitoring the postoperative immunological status.     

Expression of nm23-H1 in colorectal cancer: No association with metastases, histological stage, or survival

The correlations of nm23-H1 expression in primary cancer lesions with the already confirmed 14 prognostic variables and survival were examined in 52 advanced colorectal cancer patients, because the clinical roles of nm23-H1 expression in the cancer lesions remain controversial. An immunohistochemical expression of nm23-H1 was found in 23 lesions (positive group) but not found in 29 lesions (negative group). No significant difference between the positive and negative groups was found according to 12 clinicopathological variables including vascular invasion, lymph node and liver metastases, and histological stage. The carcinoembryonic antigen levels (21.5±33.4 ng/ml) of the draining venous blood and argyrophilic nucleolar organizer regions score (3.35±1.36 per nucleus) of the cancer cells in the positive group were not significantly different from those (34.1±102.9 ng/ml and 3.32±1.00 per nucleus, respectively) in the negative group. In addition, no significant difference was found in the survival curves or the 5-year survival rates of the positive and negative groups. From these results, it may be concluded that the nm23-H1 expression was not associated with the aforementioned prognostic variables and the prognosis of advanced colorectal cancer patients.     

The clinical usefulness of preoperative CEA determination in gastric cancer

Between 1980 and 1984, preoperative serum carcinoembryonic antigen (CEA) was determined in 468 patients with gastric cancer to evaluate its clinical usefulness. The positive rate of preoperative CEA was 20.9 per cent in these 468 patients. A significantly higher CEA positive rate was obtained in those patients with liver metastasis (69.2 per cent), n3-4 (40.0 per cent), stage IV gastric cancer (37.0 per cent) and Pap, Tub1 histological type (26.3 per cent) (p less than 0.01). It is interesting that the positive rate of the 49 unresectable patients was 51.0 per cent, which was significantly higher than 17.4 per cent of the 419 resectable cases (p less than 0.01). CEA levels in 16 of the 39 patients with liver metastasis were more than 100 ng/ml. In contrast, serosal invasion and peritoneal metastasis were less correlated to the CEA positive rate. In the 419 resected cases, the 5 year survival rate in the higher CEA group of more than 50 ng/ml (35 cases) was 4.4 per cent, which was significantly lower than 64.0 per cent in the negative group (346 cases) (p less than 0.01). These results show that CEA determination in patients with gastric cancer is useful for the prediction of prognosis, as well as for a diagnostic tool to discover the presence of liver or lymph node metastasis.     

Carcinoembryonic antigen to detect hepatic metastases of colorectal cancers

Purpose. The spread of colorectal carcinoma (CRC) affects both staging and treatment. In this prospective study we examined the relationship between carcinoembryonic antigen (CEA) levels in bile, mesenteric venous blood, and peripheral venous blood, and the presence of occult hepatic metastases in patients with CRC.Methods. Sixty patients who underwent elective surgery at Ankara Oncology Hospital were voluntarily assigned to one of the three groups of 20 patients each. The control group consisted of patients operated on for benign biliary disorders, the second group consisted of patients with CRC without metastases, and the third group consisted of patients with CRC and isolated liver metastases. Bile, mesenteric venous blood, and peripheral venous blood was collected perioperatively for the measurement of CEA levels.Results. The bile CEA levels were significantly higher in the CRC patients with metastases than in those without metastases and the controls. The CEA levels in the mesenteric venous blood and peripheral venous blood were significantly higher in the two groups of CRC patients than in the control group. Overt hepatic metastases later developed in seven patients from the CRC without metastases group who had relatively high CEA levels, but the difference was not significant.Conclusion. The CEA levels in bile, mesenteric venous blood, and peripheral venous blood were increased in patients with CRC and liver metastases. The detection of elevated CEA levels in bile taken at surgery did not herald metachronous hepatic metastases in CRC patients without liver metastases.     

手术操作对胃癌细胞外周血播散的影响及其危险因素

目的研究手术操作对胃癌细胞外周血播散的影响及其危险因素。方法45例胃癌患者于胃癌根治手术前后即刻分别取外周血,采用RT-PCR的方法测定外周血中癌胚抗原(CEA) mRNA的表达情况。10例健康体检者和3例因胃溃疡而行胃大部切除术者为对照组。结果胃癌患者手术后CEA mRNA阳性率[48.9%(22/45)]显著高于手术前[8.9%(4/45)](P=0.000);对照组外周血CEA mRNA的表达皆阴性。手术后CEAmRNA阴性组手术时间(2.46±0.51)h,阳性组则为(3.19±0.48)h,P=0.000;早期胃癌组CEA mRNA阳性率10.0%(1/10),进展期胃癌组CEA mRNA阳性率54.8%(17/31),P=0.034;差异均有统计学意义。多因素Logistic回归分析显示,手术时间和肿瘤侵犯深度为手术后CEA mRNA阳性率升高的危险因素。结论手术操作可导致胃癌肿瘤细胞播散进入血液循环,手术时间和肿瘤侵犯深度为重要的危险因素,随着手术时间的延长和肿瘤侵犯深度的增加,肿瘤细胞播散入血的可能性增加。     

Mitotic activity of cancer in the colorectum: correlation with histopathologic variables and survival

An in vivo stathmokinetic method was used to analyze the mitotic activity (MA) of cancer cells from 43 colorectal cancer patients in order to examine the correlation between MA, and histopathologic variables and survival of patients. Significant relationship was not found between MA and 7 variables of cancer lesions consisting of tumor size, macroscopic type, depth of invasion, venous and lymphatic invasion, node metastasis and stage. However, tumor differentiation was significantly related to MA: mitotic indices (MI, mean +/- S.D.) were 20.7 +/- 8.8% in 37 differentiated adenocarcinomas and 38.2 +/- 8.4% in 6 undifferentiated adenocarcinomas. The latter was significantly (p less than 0.001) higher than the former. The survival curve of 23 patients with low MA (MI less than 20.0%) was significantly (generalized Wilcoxon test, Z = 2.17, p less than 0.05) better than that of 17 patients with high MA (MI greater than 20.0%), though difference in 2 (lymphatic invasion and tumor differentiation) out of 12 variables of background was found between them. The survival curve of 17 patients with differentiated adenocarcinoma of low MA also was significantly (Z = 1.98, p less than 0.05) better than that of 17 patients with differentiated adenocarcinoma of high MA, even though no significant difference of 12 variables in background was found between them. These results suggest that MA of cancer cells may be independent of prognostic variables of cancer lesions and may be utilized as a new prognostic variable of colo-rectal cancer.     

结直肠癌患者中性粒细胞淋巴细胞比值和T淋巴细胞CD69变化的意义

目的:探讨结直肠癌患者术前外周血中T淋巴细胞CD69、中性粒细胞淋巴细胞比值(NLR)变化的意义.方法:选取2016年5月—2018年12月我院收治的126例结直肠癌患者(病例组)、120例结肠息肉患者(对照组);检测两组的术前外周血中T淋巴细胞CD69、NLR,分析不同临床病理学特征的结直肠癌患者T淋巴细胞CD69、...     

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??Recent advancement in metastasis of gastric cancer XU Hui-mian, XU Yan. Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang 110001, China
Corresponding author: XU Hui-mian, E-mail:xuhuimian@126.com
Abstract Metastases of gastric cancer includes lymph node, peritoneal and blood metastasis serially according to the incidence. Depth of tumors invasion, macroscopic type, tumors >4cm in diameter, poor-differentiated and the presence of lymphatic invasion are important determinants of the lymph node metastasis. Lymph node metastasis is the most important prognostic factor for early gastric cancer. The cytological detection of exfoliated cancer cells (ECCs) is the criterion for identifying risk of peritoneal metastasis. Macroscopic serosal classification can be used to be a predictor of peritoneal recurrence. Carcinoembryonic antigen (CEA) and heparanase have been considered the valuable indicator to predict peritoneal metastasis. Gastric cancer with elevated type, well-differentiated, hepatoid adenocarcinoma and the presence of venous invasion are associated with liver metastasis. The characteristics of gastric cancer with lung or bone metastasis include the infiltrating carcinoma, poor-differentiated and the presence of venous invasion.