High CEA Level Research Articles

Clinical evaluation of tumor targeting with the anticarcinoembryonic antigen murine monoclonal antibody fragment, MN-14 F(ab)2.

The initial clinical experience with the second-generation, high-affinity, MN-14 immunoglobulin (IgG) anticarcinoembryonic antigen (CEA) monoclonal antibody (MoAb) in patients with CEA-producing tumors was reported previously. A bivalent fragment of this MoAb, MN-14 F(ab)2, was prepared, and its pharmacokinetics, targeting properties, dosimetry, and immunogenicity were investigated. MN-14 F(ab)2(0.6-29 mg) was labeled with 131I(7.7-269 millicuries and injected into 28 patients with CEA-producing cancers. External scintigraphy was used to evaluate tumor targeting. Quantitative external scintigraphy methods were used to determine the organ and tumor radiation doses. The overall sensitivity of tumor targeting on a lesion basis was 86%, similar to that reported previously for MN-14 whole IgG. The biologic T1/2's for the fragment in the blood and total body (in hours) were 16.8 +/- 4.1 and 59.4 +/- 9.4, respectively, compared with 27.3 +/- 15.7 and 69.6 +/- 32.2 reported for MN-14 IgG. Depending on the protein dose given, high plasma CEA levels (>100ng/ML) resulted in a significant alteration of MoAb pharmacokinetics and organ dosimetry. Individual tumors received an average dose of 10.7 +/- 7.3 centigray [cGy]/mCi, and the tumor-to-total body, red marrow, lung, liver, and kidney dose ratios were 16.8 +/- 11.1, 5.6 +/- 3.6, 5.1 +/- 3.9, 6.0 +/- 3.8, and 3.1 +/- 2.0, respectively (mean + standard deviation [SD]). Only 9 of 18 patients (50%) injected with >4 mg (range: 4-52.1 mg) of MN-14 F(ab)2 developed significant levels of human antimouse antibodies, suggesting that the F(ab)2 may be less immunogenic than the intact IgG. MN-14 F(ab)2 exhibits a similar targeting sensitivity and tumor dose as reported previously for the IgG form. The lower red marrow doses combined with lower immunogenicity expected for this agent, may make it a suitable alternative for future imaging and therapeutic applications.

A CASE OF ADULT GIANT RETROPERITONEAL MATURE TERAYTOMA WITH SERUM HIGH LEVELS OF CEA AND CA19-9

An adult case of giant retroperitoneal matured teratoma with high serum levels of CEA and CA19-9 is described together with a review of the literature. A 20-year-old woman was seen at the hospital because of a mass in the right lateral abdomen which was detected at an artificial abortion in another hospital. On admission serum CEA and CA19-9 were as high as 59.8ng/dl and 166.2U/ml, respectively. In computed tomography and magnetic resonance imaging, the tumor was visualized as a giant multiloculated and cystic mass showing various components comprizing of fat, bone and fluid. An abdominal angiography revealed that the tumor was hypovascular in nature and encasement and tumor stain were not observed. Under a diagnosis of retroperitoneal teratoma, extirpaion of the tumor was performed. Macroscopically, the specimen was cystic multiloculated tumor, consisting of white transparent fluid and yellowish pappy materials containing hairs. The tumor was 26.5×17.5×9.3cm in size and 2.325g in weight. Examination of the tumor markers in the content showed remarkably high levels of CEA of >10, 000ng/dl and CA19-9 of >10, 000U/ml. The histological examination revealed that the tumor was matured benign teratoma with components from three germ layers. After extirpation of the tumor, serum levels of CEA and CA19-9 decreased to the normal levels. The patient has been in good health without any sign of recurrence for 18 postoperative months. The patient is followed on ambulant basis.

CEA, CYFRA21-1 and SCC in non-small cell lung cancer

CEA, SCC and CYFRA 21-1 were measured in samples of serum coming from 105 ‘Non small cell lung cancer’ (NSCLC) patients. The present study has been carried out to compare these markers, to analyse their prognostic significance and to determine the best combination of tumor markers. The median value and interquartile range were: CYFRA 21-1: 2,3 ng/ml, CEA: 3,7 ng/ml, SCC: 1,2 ng/ml. CEA demonstrated higher values in adenocarcinomas ( P = 0.04). SCC and CYFRA 21-1 were comparable in the different histologic groups. CYFRA 21-1 and CEA values were dependant on tumor stage. Advanced tumors (T3 and T4) demonstrated higher serum CYFRA 21-1 level ( P = 0.0006). CYFRA 21-1 was higher than 3,3 ng/ml in 36% of patients. CEA was higher than 5 ng/ml in 38% of patients and SCC was higher than 2 ng/ml in 27% of patients. Patients with a high CEA and CYFRA21-1 serum level had a shorter survival than those with a normal serum level. In a Cox regression analysis four variables (TNM stage, age, CYFRA 21-1 and CEA level) were found to be significant in the prediction of survival; CYFRA 21-1 level had the lowest P value ( P = 0.0002). The current study suggests the use of a combination of CEA and CYFRA 21-1 in the clinical care of NSCLC.

A prognostic value of CA 19-9 but not of CEA in patients with gastric cancer

The diagnostic and prognostic value of tumour markers CEA and CA 19-9 was studied in patients with gastric cancer. Pre-operative serum concentrations of CEA and CA 19-9 were determined in 100 gastric cancer patients and in 77 patients with relevant benign diseases. The sensitivity of both CEA (cut-off level 3 ng/ml) and CA 19-9 (cut-off level 37 U/ml) for gastric cancer was 30%. The specificities were 73% and 87%, respectively. There was a significant difference in prognosis, for both CEA (cut-off level 3 ng/ml, P < 0.05) and CA 19-9 (cut-off level 37 U/ml, P < 0.01), between patients with high vs low pre-operative serum levels. The overall 5-year survival was 26% and that of patients with low marker levels was 30% (CEA) and 35% (CA 19-9) compared with 15% (CEA) and 0% (CA 19-9) for patients with high marker levels. To evaluate whether the high vs low serum marker level was an independent prognostic factor, the patients were compared within the same stage of disease. There was still a significant difference in 5-year survival in stages II, III and IV between patients with high vs low pre-operative serum levels for CA 19-9 (P < 0.05), but not for CEA. In stage I, no differences in survival could be found for either marker. In conclusion, high pre-operative serum levels of CEA seem to predict higher stage of disease, whereas CA 19-9 might have an independent prognostic value in patients within the stage of II, III or IV gastric cancer. The diagnostic value of both CEA and CA 19-9 is limited.

Ovarian Strumal Carcinoid with Markedly High Serum Levels of Tumor Markers

We report a 54-year-old woman with ovarian strumal carcinoid in association with dermoid cyst and mucinous cystadenoma in the same ovary and who had markedly high serum levels of CEA (202 ng/ml), CA125 (710 U/ml), and CA19-9 (11,500 U/ml). These tumor markers were not found in the thyroid tissue or carcinoid by immunohistochemical methods, but their serum levels decreased to below the cutoff levels after surgery. In our case, the change of serum levels of these tumor markers may be useful for the follow-up after surgery.

下顎骨に発生した類表皮嚢胞の１例 サイトケラチンおよび嚢胞内容液分析

A case of epidermoid cyst in the mandible is reported in which the cystic lining epithelium was evaluated immunohistochemically with anti-keratin antibody. The patient was a 64-year-old man who was referred to our department due to swelling of the lower labial gingiva in the median region. The swollen lesion was clinically diagnosed as a cyst of the lower jaw, and it was surgically enucleated under general anesthesia. The cyst contained serous fluid with like-scum substances, and a high level of CEA was found. The cystic epithelium was examined immunohistochemically with anti-cytokeratin antibody. Staining of PKK2 and CK10 was positive in basal cells and parakeratinizing cells, while that of CK5 and CK19 was negative.

Prognostic value of combination assays for CEA and CA 19-9 in gastric cancer.

Preoperative serum CEA and CA 19-9 levels in 158 patients with gastric cancer were analyzed with respect to prognostic factors, using univariate and multivariate analysis. The incidence of high preoperative levels of both CEA and CA 19-9 was 10.1% (16/158). 13.9% (22/158) showed high CEA levels and normal CA 19-9 levels, whereas the reverse was true in 16.5% (26/158). Neither marker showed a high level in 59.5% (94/158). The multivariate analysis showed that in addition to tumor stage, the depth of invasion, liver metastasis and peritoneal dissemination, combination assays of preoperative serum CEA and CA 19-9 levels were an independent prognostic factor. Combination assays of preoperative serum CEA and CA 19-9 will allow us to conduct a more careful postoperative follow-up of high-risk patients, and also help determine the optimum adjuvant chemotherapy.

A CASE OF LYMPHOEPITHELIAL CYST OF THE PANCREAS

Lymphoepithelial cyst (LEC) of the pancreas is a rare condition and only about 20 cases have been reported in the world. We have reported here a case of LEC in a 63-year-old man complained of backpain with dullness and tenderness. Two cystic lesions in the pancreas head and tail respectively were found by of abdominal alteasonography, CT and magnetic resonance imaging. The cysts 10cm and 5cm in diameter were solid and did not invaded the surrounding tissue. For high levels of serum CEA and CA19-9, we could not rule out a suspicion of malignancy. Laparotomy was performed and it was revealed that the two cysts were smooth, well-circumscribed and encapsuled at surface of the pancreas head and tail. Since the cytological findings of the contents and cut surface were negative for malignancy, enucleation of the cyst of the pancreas head and distal pancreatectomy with splenectomy were carried out. The contents were keratinous material. Microscopically the wall was lined by keratinizing squamous epithelium, and it was surrounded by lymphoid tissue with focal follicles. The histologic diagnosis was LEC of the pancreas. The stains for CEA and CA19-9 of epithelial cells were positive. Postoperatively, his symptom disappeared and serum CEA and CA19-9 concentrations were normalized.

A CASE OF CECUM CANCER METASTASIZING TO THE SPLEEN AFTER RIGHT HEMICOLECTOMY

A case of cecum cancer metastasizing to the spleen ten months after a radical operation which was detected by elevated serum CEA is reported. A 56-year-old woman developed a cecum carcinoma with high serum level of CEA. Although serum CEA level had been almost normalized after right hemicolectomy, it elevated again during the follow-up period. Splenic tumor suggestive of recurrent cecum cancer was pointed out by CT scan and angiogram. Splenectomy, sampling of lymph nodes, and resection of peritoneal nodules were performed at the 2nd operation. In histology, they were moderately differentiated adenocarcinoma consistent with the primary tumor. Tumor thrombus was observed in the splenic sinus. Detection of splenic metastasis from colonic carcinoma is extremely rare during clinical course, since most splenic metastasis is found as a part of wide-spreaded metastasis in autopsy studies. Although prognosis of the patient with splenic metastasis is very poor, solitary metastasis will be indication for splenectomy. In this case hematogenous metastatic pattern was suggested.

A CASE OF PSEUDOMYXOMA PETRITONEI WHICH SHOWED MALIGNANT CHANGE DURING A 49-YEAR OBSERVATION PERIOD

A 67-year-old man with a chief complaint of a right abdominal mass was admitted in August, 1989. There was a previous history of several fisutulectomies after appendectomy in 1944. Histopathological examination of the fistula showed benign pseudomyxoma peritonei. On admission, a CT scan showed a low density tumor in the right abdominal region with a high serum CEA level. With diagnosis of possibile recurrence of pseudomyxoma peritonei, surgery for reduction was performed. Microscopic examination showed mucinous adenocarcinoma/pseudomyxoma peritonei. Serum CEA levels remained low for 5 months, but abdominal CT revealed recurrent pseudomyxoma peritonei in January, 1990. A third operation was performed for recurrence during the next three years, the tumor gradually increased, and the patient died in September 13th 1993. He survived for 49 years after initial treatment.

Detection of lymph node metastases in lung cancer: comparison of 131I-Anti-CEA-Anti-CA 19-9 immunoscintigraphy versus computed tomography

Mediastinal lymph node metastasis is one of the most important prognostic variables of lung cancer. We designed a study to compare immunoscintigraphy (IS) using iodine-131 anti-carcinoembryonic antigen (CEA) and anti-carbohydrate 19-9 (CA 19-9) monoclonal antibody and computed tomography (CT-scan), in the setting of mediastinal staging. Seventeen patients were involved in a prospective, blind study, to compare IS with CT-scan imaging of the mediastinum. Sensitivity and specificity of both methods were analyzed with reference to pathological staging by mediastinal lymph node sampling. IS imaging was not possible in two patients owing to a thyroid uptake and one patient refused surgery. Among the 14 evaluable patients, sensitivity and specificity were 0.83 and 0.12 for IS, and 0.66 and 0.50 for CT-scan, respectively. We used different thresholds of positivity for both methods in order to evaluate the sensitivity-specificity relationship. When compared with that of IS, the area under the receiver operating characteristic (R.O.C.) curves of the CT-scan was bigger. Although one patient had pathologically confirmed N2 with negative CT-scan and positive IS, the results of IS were hampered by a very high level of false positivity. Finally, there was no relationship between positivity of IS and a high serum CEA level. Lack of specificity and the insufficient sensitivity of the iodine-131 anti-CEA-anti-CA 19-9, lead to the conclusion that IS adds weak information to a CT-scan, in the non-invasive mediastinal staging of lung cancer. More efficient radionuclides and markers are needed in the setting of lung cancer staging.

A CASE OF MUCINOUS CYSTADENOMA OF THE PANCREAS WITH ABNORMALLY HIGH LEVELS OF CEA AND CA19-9 IN THE CYSTIC FLUID

We experienced a case of mucinous cystadenoma of the pancreas with abnormally high levels of CEA and CA19-9 in the cystic fluid. A 79-year-old man visited a nearby hospital because of abdominal distention after drinking alcohol and was referred to the hospital for a suspected pancreatic cyst which was revealed by ultrasonography. On admission multilocular cyst and dilated pancreatic duct were found. The patient was diagnosed as having a cystadenoma of the pancreas and underwent distal pancreatectomy. Cystic fluid was transparent mucus, and CEA and CA19-9 levels were abnormally high, 6, 700ng/ml and 84, 860U/ml respectively. Histopathologically it was mucinous cystadenoma positioning at a borderline pancreatic carcinoma. In general mucinous cystadenoma of the pancreas has a high malignant potential compared to serous cystadenoma of the organ. It possesses many problems in clinical treatment and, reportedly, CEA and CA19-9 often increase in malignant cases. For this, careful postoperative observation would be indispensable in this case, by entertaining a possible malignant change.

A CASE OF HILAR CARCINOMA OF THE BILE DUCT WITH A RECURRENCE IN THE SPLENIC FLEXURE

This paper describes a surgical resection of a solitary cystic recurrent tumor in the splenic flexure in a patient with hilar carcinoma of the bile duct, who also experienced a local recurrence one year earlier. A 56-year-old woman was admitted to the hospital because of appetite loss and left upper abdominal pain. These were previous histories of undergoing left hepatectomy and caudate lobectomy as a complete curative operation for a left hilar carcinoma of the bile duct in December 1989; and enucleation of a tumor recurring at the residual liver cut surface with a high level of CEA in September, 1991. This time CT showed an abdominal cystic tumor about 5cm indiameter in the splenic flexure, barium enema revealed a stenosis of splenic flexure due to extraserosal compression, and carcinoma cells (class V) were evidenced by the aspiration cytology. The third operation was done with a preoperative diagnosis of the recurrence of the hilar bile duct carcinoma. The tumor was placed in the omentum with invasion into to the colon, of which pathological findings were considered as the recurrence.

A CASE OF MUCINOUS CYSTADENOMA OF THE APPENDIX WITH HIGH SERUM CEA LEVEL

The appendix mucocele is a rare disease and often presents difficulty in diagnosis before operation. We experienced a case of mucinous cystoadenoma of the appendix with high serum CEA level. A 74-year-old man was admitted to the hospital because of severe dizziness due to melena. When a mass was palpable in the right lower abdominal quadrant. Gastro and colonofiberscopies revealed no cause of melena but a SMT like elevation in the cecum. Barium enema examination showed the extraluminal compression of the ascending colon, but the appendix could not be visualized. A cystic mass contacted with the right kidney was revealed by ultrasonography and CT scan. The renal cell carcinoma was suspected by fine needle aspiration biopsy. Suspected of malignancy with the high level of serum CEA, right hemicolectomy and right nephrectomy with lymph nodes dissection were performed. Histological, the tumor was mucinous cystadenoma of the appendix with no severe atypical cell. Melena was from ileal ulcer which was included in the resected lesion. After the operation, the serum CEA has smoothly fallen to normal level. This disease may result in pseudomyxoma peritonei with poor prognosis. Here the importance of the complete resection so as not to lose the time after diagnosis is emphasized.

Evaluation of the behavior of carcinoembryonic antigen in cirrhotic patients.

Benign liver diseases are a cause of increased serum levels of CEA. We studied the behavior of CEA in 86 patients with liver cirrhosis who underwent extensive clinical and laboratory evaluation. We found abnormal CEA levels in 38.4% of the patients (28.6% Child's grade A, 40.6% Child's B, and 42.4% Child's C) with a mean of 4.75 ng/ml. Significant differences were found between patients and controls. There was a trend towards higher levels of CEA in more severe cirrhosis according to Child's classification, although this was not significant. We found significant correlations between CEA and some liver tests, including glycocholic acid (r = 0.264., p = 0.012), a marker of severity in liver diseases. The increase of CEA in these patients is probably due to alterations in its metabolic processing caused by hepatocellular dysfunction. Moderate elevations of serum CEA can be expected in cirrhotic patients independently of malignancy.

A CASE OF RECTAL CANCER METASTASIZING TO THE SPLEEN

The spleen is rarely involved by metastatic carcinoma, especially by colon cancer. This paper reports a recent case of rectal cancer (Rs) with a solitary splenic metastasis.The patient was a 62-year-old male with high serum level of CEA (15.1 ng/ml). Histological examination revealed Borrmann 2 type and moderately differentiated adenocarcinoma characterized by s, n (+), INF-β, ly2, v1. Two metastatic lesions were found in the right lobe of the liver and one in the left lobe. A solitary metastasis of 5.0×4.0 cm was found in the lower pole of the spleen. In addition to anterior resection (R3), splenectomy was performed. Further the metastatic lesion in the left lobe was enucleated, and a catheter of the injection port was inserted into the right gastroepiploic artery for chemotherapy. Four months after the operation the patient is still in good health. A review of the literature showed only 13 reports on colon cancer with splenic metastases. In all these cases, preoperative serum CEA levels were extremely high. This demands consideration of possible splenic metastases in patients with high CEA values, but without hepatic or pulmonary metastasis. To say more about prognosis for such cases, further case studies will be required.

A case of pancreatic pseudocyst with high level of CEA in the cyst fluid

A case of pancreatic pseudocyst with high level of CEA in the cyst fluid

Preliminary Study on Serum Levels of Mucinous like Cancer Antigen (MCA) in Patients with Breast Disease: Comparison with CEA

MCA (mucinous-like cancer antigen) can be measured in the biological fluids of patients by means of a solid phase enzyme immunoassay. This study describes the results of MCA determination in sera of 230 patients with benign (99) and malignant (131) breast diseases. MCA levels were significantly higher in breast cancer patients than in non cancer patients and in healthy subjects (p less than 0.001). MCA concentrations tended to increase as the stage of the disease advanced. The 95th percentile of MCA value distribution in normal subjects showed a diagnostic sensitivity in breast cancer patients of 16.3% at stage I, 26.2% at stages II-III and 52% at stage IV. In a group of 118 cancer patients, MCA and CEA were tested simultaneously. The diagnostic sensitivity and specificity of MCA and CEA assays was very similar; nevertheless the association of the two tests showed 11 cases with high levels of MCA and low levels of CEA and 9 patients with high levels of CEA and low levels of MCA. Seventy-four out of 118 patients were negative for both markers and in 22 out of 118 patients markers were positive. The new marker MCA appeared to correlate with breast cancer and gave different information complementary to CEA.

NON-FUNCTIONING ISLET CELL TUMOR ACCOMPANIED BY LARGE LYMPH MODE METASTASIS

Minute non-functioning islet cell tumor accompanied by large lymph node metastasis in a 61-year-old male is reported. The patient was reffered to us because of upper abdominal pain and high CEA level in blood. Physical examination revealed abdominal tumor but close evaluation including abdominal CT and angiography failed to establish the definite diagnosis. Operation showed a fist-sized lymph node swelling beneath the pancreas suggesting metastasis. But it was impossible to identify the primary focus and only lymph node biopsy was performed. He died on 31-post-operative-day. Autopsy revealed the minute non-functining islet cell carcinoma with a 2mm diameter as the primary origin. In general, the non-functioning islet cell tumor exerts relatively low malignancy, and even in a malignant case, the primary focus grows expansively and forms a large tumor. This case seems to be a rare one developing mainly to the lymph node.

A CASE OF PRIMARY ADVANCED CARCINOMA OF THE DUODENAL BULB ASSOCIATED WITH HIGH PLASMA LEVELS OF CEA AND CA19-9

In carcinomas of the duodenal bulb, even in advanced cases, it has been reported that the level of plasma CEA or CA19-9 is almost within the normal limit. We encountered a case of carcinoma of the duodenal bulb associated with abnormal high levels of CEA and CA19-9. A 70-year-old male was admitted with the complaint of abdominal distension. Pancreatoduodenectomy was performed under a diagnosis of gastric cancer invading the duodenum. Because of the location of the main lesion at the duodenal bulb, as well as pathological findings, it was diagnosed as a primary carcinoma of the duodenal bulb. Ten months after the operation, multiple liver metastases were revealed by computed tomography, and progressed with the elevation of CEA and CA19-9 levels. Two years and ten months after the operation, he was expired from liver dysfunction. Immunohistological staining for CEA and CA19-9 using monoclonal antibody showed positive responses in themain lesion and metastatic lesions. There findings suggest that cancer tissue may produce CEA and CA19-9.