Low Carcinoembryonic Antigen Level Research Articles

Hepatectomy for Peripheral Cholangiocarcinoma in Elderly Patients

Peripheral cholangiocarcinoma (CCC) is less common than hepatocellular carcinoma. Little is known about CCC patients older than 70 years who have undergone hepatectomy. Between 1977 and 2004, the clinical features of 33 elderly CCC patients (>70 years old) undergoing hepatectomy were reviewed, and 185 CCC patients younger than 70 years (younger CCC) were used for comparison. A total of 218 CCC patients undergoing hepatectomy were investigated with ages ranging from 28 to 93 years (median, 59.0 years). The elderly and younger CCC groups had a similar sex ratio and a similar positive rate of carcinoembryonic antigen (CEA) and CA19-9. A similar rate of hepatolithiasis, mucobilia, papillary pattern, stage distribution, curative hepatectomy, surgical morbidity, and mortality for CCC were also observed between the two groups. During a follow-up duration ranging from 1.1 to 145.0 months (median, 11.7 months), elderly CCC and younger CCC patients had similar prognoses after hepatectomy (P = .827). Elderly CCC patients with a low CEA level, an intraductal papillary growth pattern, curative hepatectomy, and postoperative chemotherapy tended to have favorable survival. However, elderly CCC patients with a low CEA level independently showed favorable survival. Hepatectomy is feasible for selected elderly CCC patients. Elderly CCC patients undergoing hepatectomy had clinicopathologic features and prognoses similar to those of patients younger than 70 years undergoing hepatectomy. Elderly CCC patients with a low CEA level, intraductal papillary growth pattern, curative hepatectomy, and postoperative chemotherapy tended to have favorable survival. However, elderly CCC patients with low CEA level independently showed favorable survival.

EUS-FNA of Cystic Pancreatic Tumors

Due to limitations with diagnostic imaging alone, endoscopic ultrasound (EUS)-guided fine needle aspiration (EUS-FNA) of pancreatic cyst fluid provides additional information to help characterize these lesions as inflammatory, benign, premalignant, or malignant. When greater than 2 mL of cyst fluid is obtained from EUS-FNA, the following should be examined: cytology, carcinoembryonic antigen (CEA), and amylase. Pseudocyst fluid generally has thin viscosity, is yellow to brown in color, and has low CEA and elevated amylase levels. Fluid from serous cystic neoplasms is thin, colorless with a low CEA (<200 ng/mL), and low amylase levels. Aspirates from mucinous cystic neoplasms (including intraductal papillary tumors [IPMTs]) are generally viscous with an elevated CEA (>200 ng/mL) but variable amylase levels. Complications following EUS-FNA of these lesions occur in 1% to 2% of patients and may be minimized by performing only one pass, completely aspirating the punctured cyst, and administration of antibiotics.

Clinicopathological study of cardiac tamponade due to pericardial metastasis originating from gastric cancer

To review the cases reported in the literature, examined their clinicopathological features, and evaluated the efficacy of different therapeutic modalities for this rare condition. A search of the MEDLINE database revealed 16 cases of pericarditis carcinomatosa (PC) originating from GC reported in the literature between 1982 and 2005. Additional detailed data were obtained from the authors of these studies for subsequent clinicopathological investigation. We have also described about a case study from our own clinic. The mean age of cases with pericarditis carcinomatosa originating from GC was 54 years. Females were diagnosed at a younger age (46.3 years) compared to males (58 years). The mean survival period after diagnosis was 4.5 mo. No statistical differences in the length of survival time were found between different therapeutic modalities, such as drainage, and local and/or systemic chemotherapy after drainage. However, three cases who underwent systemic chemotherapy survived for more than 10 mo. Cases that developed metachronous cardiac tamponade for more than 2 years after the diagnosis of GC generally survived for a longer period of time, although this was not statistically significant. Multivariate analysis revealed that low levels of carcinoembryonic antigen (CEA), and CEA and/or cancer antigen 19-9 (CA 19-9) were associated with longer survival. Cases with low levels of CEA, and CEA and/or CA 19-9 should undergo systemic chemotherapy with or without local chemotherapy after drainage.

Preoperative serum levels of the carcinoembryonic antigen in hereditary non-polyposis colorectal cancer compared to levels in sporadic colorectal cancer

Background: Carcinoembryonic antigen (CEA) serves as the most widely used and most cost-effective tumor marker in colorectal cancer for almost 30 years. Recent publications about serum CEA levels are based on patient groups without definite differentiation between hereditary and non-hereditary forms of colorectal cancer. Patients and methods: We compared preoperative CEA serum levels from 105 patients with hereditary non-polyposis colorectal cancer (HNPCC) and 107 patients with sporadic colorectal cancer including influences of age and Dukes stage. CEA values in cases of HNPCC were correlated to the findings of microsatellite analyses, mutation analyses of the MMR genes (MLH1, MSH2) and respective immunohistochemistries. Results: Thirty-three HNPCC patients (31%) and 37 patients with sporadic CRC (34%) revealed elevated CEA levels higher than 5 ng/ml. The mean preoperative CEA level in all Dukes stages of HNPCC patients was lower with 31.7 ± 180 ng/ml than in sporadic colorectal cancer with 68.3 ± 424 ng/ml, but without significance ( p = 0.72). HNPCC tumors with signs of de-differentiation (G3 and G4) revealed significantly higher CEA values with 62.2 ± 262 ng/ml in comparison to well-differentiated tumors (G1 and G2) with 5.0 ± 9.6 ng/ml ( p = 0.02). HNPCC patients with “classical characteristics” (high microsatellite instability (MSI), MMR gene mutation, loss of MMR protein expression) had lower preoperative CEA serum levels than those without equivalent genetic alterations, but without reaching statistical significance. CEA levels of HNPCC tumors increased significantly under occurrence of metastases with mean values of 170.3 ± 343 ( p < 0.02). Conclusions: Normal preoperative serum CEA levels do not have the same validity for all colorectal cancer patients. Low CEA levels in HNPCC patients could occur due to well-differentiated tumors and should be considered more critically than in sporadic CRC patients. Further studies including comparison of postoperative CEA development are necessary to elucidate the importance of these results.

Postoperative serum carcinoembryonic antigen levels in patients with pathologic stage IA nonsmall cell lung carcinoma: subnormal levels as an indicator of favorable prognosis.

Elevated serum carcinoembryonic antigen (CEA) levels are sometimes attributable to the production of CEA by malignant cells, and in turn, the antigen itself can enhance the metastatic potential of malignant cells. The authors speculated that low serum CEA levels might be indicative of relatively low levels of malignant cells and a low probability of disease recurrence. This hypothesis led them to investigate whether low CEA levels in serum represented a useful prognostic factor for patients with pathologic Stage IA nonsmall cell lung carcinoma. Between 1993 and 2001, 724 patients underwent surgery for NSCLC at Toneyama National Hospital (Toyonaka, Japan). Of these patients, the 242 who were diagnosed with pathologic Stage IA disease were included in the current study. Smoking behavior, gender, age, tumor diameter, disease histology, and preoperative and postoperative serum CEA levels were chosen as study variables, with the cutoff level between subnormal and normal serum CEA levels set at 2.5 ng/mL and the cutoff level between normal and high serum CEA levels set at 5.0 ng/mL. Prognostic indicators were evaluated using a Cox hazard model. In addition, survival probabilities were calculated using the Kaplan-Meier method, and differences in survival were assessed by log-lank analysis. Subnormal postoperative serum CEA levels were found to be an independent prognostic indicator (hazard ratio, 2.3; 95% confidence interval, 1.1-4.7; P = 0.03 for comparison with patients who had normal CEA levels) on multivariate analysis. Furthermore, the 5-year survival rate was 87% for patients with subnormal postoperative CEA levels (n = 146), compared with 75% for patients with normal postoperative CEA levels (n = 80) and 53% for patients with high postoperative CEA levels (n = 16) (P < 0.0001). Among patients with pathologic Stage IA NSCLC, those who had an extremely favorable prognosis were distinguished by their subnormal postoperative serum CEA levels.

Prognostic factors for patients with metastatic colorectal cancer receiving protracted venous infusion of 5-FU.

The objective of this study was to investigate the possible prognostic factors in patients with metastatic colorectal cancer (CRC) treated with protracted venous infusion (PVI) of 5-fluorouracil (5-FU). PVI of 5-FU is considered to be one of the standard therapies for patients with CRC because of its high efficacy and low toxicity, but possible prognostic factors in patients with CRC treated with PVI of 5-FU have not been reported until now. One hundred two consecutive patients with metastatic CRC, treated with PVI of 250 mg/m(2) /d of 5-FU at the National Cancer Center Hospital between January 1991 and December 1998, were investigated retrospectively. The data were evaluated for possible correlations with clinicopathologic indices or prognosis. In this study, grade III nausea, stomatitis, diarrhea, and hand-foot syndrome occurred in only 3%, 5%, 5%, and 6% of cases, respectively. No grade III or more hematologic toxicities were observed. The overall response (complete response + partial response) rate for all 102 cases was 26%, with a 95% CI of 18% to 35%. Overall median survival time for the 102 cases was 303 days. In multivariate analysis, the favorable prognostic factors were normal albumin level (<or=3.7 g/dl), histologic grades I, II, and low carcinoembryonic antigen level (<100 ng/ml).

Inhibition of endogenous carcinoembryonic antigen (CEA) increases the apoptotic rate of colon cancer cells and inhibits metastatic tumor growth.

It has been suggested that carcinoembryonic antigen (CEA) enhances metastatic seeding of colon cancer cells due to its homo- and heterophilic binding properties. Our recent finding that endogenous CEA protects colon cancer cells against apoptosis suggests a more complex role of CEA in cancer progression. In this study we compared the in vitro effects of endogenous CEA on tumor cell aggregation and cell cycle regulation of human HT29 colon cancer cells with the corresponding in vivo effects, i.e. tumor cell seeding and formation of metastatic lesions. Stable expression of CEA targeted ribozymes (Rz) under control of a tet-off promoter system allowed regulation of CEA levels on the mRNA and protein level by 50%. Downregulation of CEA levels inhibited tumor cell aggregation by 70%. In accordance with previous studies, reduction of CEA levels increased in vitro the apoptotic rate and reduced colony formation by 30% to 50%. To determine the in vivo effect of CEA-dependent aggregate formation and its growth regulating role under apoptotic stress, HT29 cells with high and low CEA levels, respectively, were injected into nude mice. Immunostaining of lung microsections revealed similar numbers of tumor cells one hour after injection. 24 h later virtually all cells were removed from the lung in both groups. However, after 6 weeks all doxycycline treated mice (Rz off = CEA high) showed 14.5 +/- 4.6 metastatic lung lesions/mouse while 0.2 +/- 0.2 lesions/mouse appeared in the untreated group (Rz on = CEA low) (P < 0.001). Our study demonstrates a multifunctional role of CEA and indicates a prometastatic role of CEA independent of its adhesive function possibly due to its anti-apoptotic function.

Expression of carcinoembryonic antigen in peripheral- or central-located small cell lung cancer: its clinical significance.

Small cell lung cancer (SCLC) has a higher percentage of hilar masses than other histological types of lung cancer. The primary site is usually adjacent to the hilum, but we often observe primary sites in the peripheral lung field. In this study, our objectives were to elucidate whether peripheral-located small cell lung cancer (PSCLC) is an independent entity and whether it differs clinically from central-located small cell lung cancer (CSCLC). We reviewed the clinical and pathological features of 52 patients treated at Kagawa Medical University Hospital between 1987 and 1996 with a diagnosis of SCLC. We defined CSCLC as a tumor whose primary site is located in the segmental bronchi or more proximally and PSCLC as a tumor located distal to the subsegmental bronchi. Twenty-one PSCLC patients and 31 CSCLC patients were identified. Kaplan-Meier survival curves were constructed and comparisons were made between PSCLC and CSCLC by the log-rank test. The carcinoembryonic antigen (CEA) level was also evaluated in each group. Although the percentage of limited disease (LD) in the patients with PSCLC was higher than that in the patients with CSCLC, the 3-year survival rate of PSCLC tended to be worse than that of CSCLC (9% for patients with PSCLC and 29% for those with CSCLC). Survival curves of patients with PSCLC also tended to be worse than those of patients with CSCLC, not only in the limited disease group but also in the extensive disease (ED) group. In addition, the mean CEA value in patients with PSCLC was higher than that in patients with CSCLC (p < 0.001), whereas the neuron specific enolase (NSE) level was not significantly different between PSCLC and CSCLC. The median survival of patients with pretherapeutic CEA titers of > or =5 ng/ml was significantly shorter than that in patients with CEA levels <5 ng/ml. These findings suggest that the survival of SCLC patients with a high CEA level was significantly shorter than that of patients with a low CEA level. In addition, CEA levels in PSCLC patients were significantly higher than those in CSCLC patients. However, the survivals of LD or ED patients with PSCLC and CSCLC were not statistically different.

Diagnostic Value of CYFRA 21–1 Tumor Marker and CEA in Pleural Effusion Due to Mesothelioma

The aim of our study was to assess the clinical value of CYFRA 21-1 tumor marker and carcinoembryonic antigen (CEA) as diagnostic tools that are complementary to cytology in the diagnosis of malignant mesotheliomas. We measured CEA and CYFRA 21-1 in the pleural effusions (PEs) and serum of 106 patients (benign lung disease, 34 patients; bronchogenic and metastatic carcinoma, 40 patients; mesothelioma, 32 patients). CEA and CYFRA 21--1 levels were determined by means of two commercial enzyme immunoassays. The cutoff levels of CYFRA 21--1 and CEA in malignant PEs, selected on the basis of the best diagnostic efficacy, were 41.9 ng/mL and 5.0 ng/mL, respectively. In all neoplastic PEs, CYFRA 21--1 and CEA sensitivity was 78% and 30.6%, respectively, with a specificity of 80% and 91%, respectively. The sensitivity of CYFRA 21--1 and CEA in patients with mesothelioma was 87.5% and 3.1%, respectively. The results of the CYFRA 21--1 assay were positive in 17 of 19 cases of mesothelioma (89.5%) with a negative or uncertain cytology. The association of the tumor marker assay and the cytology allowed a correct diagnosis in 30 of 32 cases of mesothelioma (93.7%). This study suggests that CYFRA 21--1 would provide a useful parameter for the differential diagnosis between benign and malignant PE from mesothelioma when the result of cytology is negative or uncertain and the clinical context does not allow a more aggressive approach. Moreover, the association of CYFRA 21--1 with CEA could provide details for a differential diagnosis between mesotheliomas and carcinomas. In fact, an elevated CYFRA 21--1 level with a low CEA level is highly suggestive of mesothelioma, whereas high levels of CEA alone or high levels of both the markers suggest a diagnosis of malignant PE, excluding mesothelioma.

The significance of NSE and CEA as a differentiation marker for the cellular heterogeneity of small cell lung cancer.

Neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) levels in the culture supernatant of the 65 pulmonary carcinoma cell lines: Small cell lung cancer (SCLC) 18, large cell carcinoma 14, squamous cell carcinoma 14, adenocarcinoma 14 and adenosquamous cell carcinoma 5, were measured by a radioimmunoassay (RIA). The mean value of NSE was 30.8+/-22.4 ng/ml and 9.2+/-8.7 ng/ml in SCLC and non-SCLC, respectively. The mean value of CEA was 15.1+/-20.9 ng/ml and 26.6+/-72.3 ng/ml in SCLC and non-SCLC, respectively. A significant difference in NSE levels was obtained between SCLC cell lines and non-SCLC cell lines. In SCLC cell lines, a significant inverse proportional correlation was observed between NSE and CEA levels. The CEA production tended to be higher in cells with low levels of NSE than in those with high NSE production. With respect to correlation between marker production and growth characteristics of SCLC cells in vitro, significantly higher NSE and lower CEA levels were found in cells growing with floating colony or neurite like characteristics (classic cell type) than those in cells with epithelial or intermediate growth characteristics (variant cell type). A significant positive correlation between NSE levels and the survival periods was found in follow-up studies of 10 patients who underwent surgery with complete resection of the primary tumor. All of 4 long term survivors over 3 years after surgery had significantly high NSE and relatively low CEA producing tumors. The relationship of these markers to clinical status of the patient suggests that an analysis for correlation of NSE and CEA levels in SCLC patients may be useful to discriminate between a pure neuroendocrine SCLC tumor and a mixed small cell/large cell tumor, and in monitoring therapeutic effect and prognosis of each patient.

Molecular Genetics and In Vitro Sensitivity of a New Human Cell Line, KKP, from a Gastric Adenocarcinoma

A new cancer cell line (KKP) was established from an ascitic effusion of an advanced gastric adenocarcinoma, intestinal type. The line has been maintained in continuous monolayer culture with a doubling time of 48 hours for more than 2 years. KKP cells, whose ultrastructural features are presented, showed an aneuploid DNA content, a modal number of 53 chromosomes, and the presence of one double minute chromosome. The karyotype showed trisomies of chromosomes 7, 12, 13, and 14, tetrasomy of chromosome 18, a reciprocal translocation [t(1;20)(q21;p11.2)], and a [t(4;?)] rearrangement. No amplification or rearrangements were evident in the c-MYC, c-ERB B2, H-RAS, INT-2, HST-1, c-MOS, and K-RAS genes, whereas somatic rearrangements were present in the sequences corresponding to c-MET and cyclin E genes by Southern blotting analysis. Polymerase chain reaction–single strand conformation polymorphism (PCR-SSCP) analysis of P53 and RB genes did not reveal alterations or point mutations in the SSCP pattern of conformers. The chemosensitivity pattern assay of the KKP cell line indicated that it was sensitive to cisplatin, etoposide, and doxorubicin and resistant to 4′-hydroperoxycyclophosphamide. The clinical history of the patient from whom the cell line was derived is reported and compared with the results observed in the cell line in vitro. High levels of the tumor-associated antigens CEA (carcinoembryonic antigen) and CA19-9 were evident in the KKP cytosol, whereas the KKP spent culture medium maintained the same low levels of CEA and CA 19-9 found in the patient’s serum. This new cell line may represent a useful tool for studying the biology of gastric cancer and for planning new therapeutic approaches.

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.

Resection of colorectal liver metastases: 25-year experience.

The aim of this retrospective study was to analyze survival and prognostic factors in 111 consecutive patients undergoing curative resection of liver metastases from colorectal cancer. In addition, the time periods 1971-1984 and 1985-1995 were compared; criteria for first liver resection did not change with time, whereas the attitude toward re-resection was more aggressive during the latter period. Operative mortality was 6% during 1971-1984 and 0% during 1985-1995 (3.6% for all patients). The crude 5-year actuarial survivals were 19% and 35% for patients operated during 1971-1984 and 1985-1995, respectively (25% for the whole period). Relapse at any site was observed in 52 patients (81%) operated during the first period and in 29 patients (67%) operated during the second period; re-resection was performed in 12 (23%) and 15 (52%) of these patients, respectively. Five-year survival after hepatic re-resection was 29% (no operative mortality). In the univariate analysis, significant determinants for long-term survival were, in descending order, a clear resection margin, high degree of fibrosis around the tumor, absence of extrahepatic metastases (including metastases to the liver hilum), use of an ultrasound dissector, low preoperative serum carcinoembryonic antigen (CEA) level, year of resection (1985-1995), and low/moderate grade of liver tumor. There were no 5-year survivors when extrahepatic metastases were present, the liver tumor(s) had a low differentiation or satellites, or the resection margin was involved with tumor. In the multivariate analysis, the determinants were grade of liver tumor, absence of extrahepatic tumor, few intraoperative blood transfusions, low preoperative serum CEA level, and year of resection (1985-1995). It is concluded that: (1) an increased rate of hepatic re-resection was partly responsible for the improved outcome after liver resection for colorectal metastases during recent years; (2) patients with extrahepatic metastases did not benefit from liver resection; and (3) surgery should be performed with a clear resection margin and minimal blood loss.

IMMUNOBIOLOGICAL MONITORING OF VARIOUS GASTROINTESTINAL AND PRIMARY HEPATIC MALIGNANCIES

Carcinoembryonic antigen (CEA) and alpha fetoprotein levels (AFP) were assayed by enzyme-labelled immunoassay in 75 cases of gastrointestinal (GI) and primary hepatic malignancies. Mean CEA levels were found to be significantly higher (p<0.005) in metastatic non-operative group of GI malignancies (range 5.32 ng/mL to 175.2 ng/mL) as compared to early pre-operative cases (range 1.25 ng/mL to 33.2 ng/mL) and post-operative cases (range 1.41 ng/mL to 22.24 ng/mL). Variable levels of AFP were visualised in 12 cases of primary hepatic malignancies with eight cases having values less than 100 ng/mL. When both CEA and AFP were assayed simultaneously, the markers were helpful in differentiating cases of primary hepatic malignancies with low levels of CEA from 3 cases of secondaries in the liver where CEA levels were found to be highly raised (80.4 ng/mL to 146.4 ng/mL). To evaluate the variation of CEA and AFP levels in different patients having same stage of the disease, immunological monitoring for the functions of T and B cells was carried out by estimation of cytokine, i.e. interleukin-1 alpha (IL-1a), interleukin-2R (II-2R) and various immunoglobulins. IL-1a and 1L-2R levels were significantly higher (p<0.05) in the groups of patients having higher CEA and AFP. This indicates an important T cell (TH1 and TH2) function in the tumour antigen production.

Surgical resection of pulmonary metastases from colorectal carcinoma. Five-year survival and main prognostic factors.

Between 1986 and 1994, 19 patients underwent pulmonary resection for metastatic colorectal carcinoma. The mean interval between colon resection and appearance of pulmonary metastasis was 41 +/- 21 months. All the patients had no more than two metastases. Wedge resection alone or associated with lobectomy was performed in four patients, lobectomy in ten, and pneumonectomy in five. One patient died within the month after surgery. Mean follow-up was 35 +/- 26 months. The 5-year survival rate was 38.7%. Repeat thoracotomy for recurrent metastases was performed in one patient. The disease-free interval, the size of metastases, the type of pulmonary resection, and the location and the stage of primary cancer had no apparent influence on survival, but the survival rate at 4 years was 25% for patients with high carcinoembryonic antigen (CEA) level versus 80% for those with low CEA level. We conclude that, at least when the number of metastases is less than two, resection of colorectal lung metastasis is safe and effective.

Carcinoembryonic antigen levels in the peritoneal cavity: useful guide to peritoneal recurrence and prognosis for gastric cancer.

At the time of laparotomy, peritoneal washings were collected from 155 gastric cancer patients and the levels of carcinoembryonic antigen (CEA) determined. The CEA levels in peritoneal washings were statistically independent of those in sera and could more reliably predict the presence of peritoneal metastasis than a cytologic study. Peritoneal recurrence was seen in 14 of 118 patients after curative operation. Of the 14 patients, 10 (71%) had elevated levels of CEA (100 ng/g protein) at surgery. Of these 10 cases, 2 of the tumors were classified as stage IB and 4 had no serosal invasion. Only one patient with peritoneal metastasis and a low CEA level was free from relapse more than 1 year after operation. Kaplan-Meier's analysis showed that a high CEA level in peritoneal washings was a predictor of poor prognosis in patients who underwent either curative or noncurative resection. A proportional hazards regression analysis showed that a high CEA level in peritoneal washings was statistically significant in terms of predicting a shorter interval until peritoneal recurrence (p = 0.0002) and for survival (p = 0.0001). The CEA level in peritoneal washings is therefore of value as an indicator of peritoneal recurrence and prognosis.

P53 nuclear overexpression: an independent predictor of survival in lymph node--positive colorectal cancer patients.

This study was performed to determine the prognostic significance of p53 gene overexpression in a homogeneous group of node-positive colorectal cancer patients. Paraffin sections from the primary tumors in 107 colorectal cancer patients who had preoperative serum carcinoembryonic antigen (CEA) levels less than five were examined for the expression of p53 nuclear protein by immunohistochemical staining using the monoclonal antibody PAb 1801. The nuclear p53 overexpression was compared with clinicopathologic variables and follow-up data. Positive staining was not observed in normal colorectal mucosal cells. Specific p53 nuclear staining was detected in primary tumor from 50 patients (46.7%). p53 nuclear overexpression was not significantly correlated with patients' sex, age, tumor location, differentiation, T stage, N stage, and lymphatic and/or vascular vessel invasion. With a median follow-up of 61.7 months, 60% of the p53-positive patients have had disease recurrence, versus only 35% of the p53-negative group (P = .02). Forty-two percent of the p53-positive patients died of colorectal cancer compared with 21.1% of the p53-negative patients (P = .03). By multivariate analysis, p53 overexpression was found to be an independent predictor for disease-free and disease-specific survival. In node-positive colorectal cancer patients with low preoperative CEA levels, nuclear p53 overexpression as determined by immunohistochemistry on archived tissue is an independent predictor for prognosis.

Carcinoembryonic antigen in fine‐needle aspirate of liver: A diagnostic adjunct to cytology

Carcinoembryonic antigen (CEA) was measured in 50 consecutive fine-needle aspirates of liver to determine whether elevated levels could predict the presence of carcinoma in cytologically negative aspirates. There were 44 malignant and 6 benign lesions. The highest mean CEA values (591-672 ng/ml) were obtained in metastatic adenocarcinoma of the colon, stomach, and pancreas; lower levels (13.5-151 ng/ml) were found in metastatic carcinoma from the breast and lung. Carcinoid, hepatoma, Hodgkin's disease, and benign liver aspirates had low (less than 5 ng/ml) CEA levels. Cytologic diagnosis of malignancy was 96% sensitive and 100% specific. Using 5 ng as a cutoff for malignancy, the overall sensitivity of CEA for detection of malignancy was 77%; for detection of adenocarcinoma alone, sensitivity was 85%. Specificity was 100%. The CEA content of fine-needle aspirates generally exceeded serum values by 10-100-fold. Although CEA content did not enhance the sensitivity of cytologic diagnosis, it may suggest metastatic carcinoma of the GI tract in patients presenting with adenocarcinoma of an unknown primary source.

Measurement of CA125, carcinoembryonic antigen, and alpha‐fetoprotein in ovarian cyst fluid: Diagnostic adjunct to cytology

This study used CA125, carcinoembryonic antigen (CEA), and alpha-fetoprotein (AFP) to classify ovarian cysts by measuring the levels of the three antigens; this information was useful when fluid obtained through laparoscopic puncture of ovarian cysts was submitted for cytologic examination from patients for whom tissue was unavailable for classification. We studied 136 consecutive cyst fluids (108 benign, 28 malignant) and correlated the findings with the tissue diagnosis. All three antigens were very low (CEA, less than 0.5 ng/ml; CA125, 55-2,143 mu/ml; and AFP, less than 4.8 ng/ml) in follicular and lutein cysts. Markedly elevated CA125 (296-1,950,000 mu/ml) and low CEA (0.5-220 ng/ml) and AFP (less than 4.8 ng/ml) levels were seen in patients with serous neoplasms, both benign and malignant. Elevated CEA (greater than 600 ng/ml) and CA125 (56-65,330 mu/ml) levels were seen in primary mucinous cystadenoma and cystadenocarcinoma. Two patients with colonic carcinoma metastatic to the ovary had an elevated CEA (greater than 600 ng/ml) and a normal CA125. Only one patient, with a malignant teratoma, had an elevated AFP. The adjunctive use of CEA and CA125 is recommended for the classification of ovarian cysts.

The effect of serum CEA on the distribution and clearance of anti-CEA antibody in a pancreatic tumour xenograft model

A human pancreatic adenocarcinoma was used to develop two histologically distinct xenograft lines, one associated with high levels (180-2000 ng ml-1) and one with low levels (greater than 2.0 less than 8.0 ng ml-1) of serum carcinoembryonic antigen (CEA). A strong correlation was found between tumour size and both circulating and tumour CEA levels in the former group, and also correlation at the 5% level between tumour size and serum CEA in the latter. Administration of either monoclonal or polyclonal 125I-anti-CEA antibody led to the formation of intravascular antigen-antibody immune complexes in mice with high CEA levels, and these were rapidly cleared by the liver, deiodination commencing within the first hour. Blood activity was reduced to 20% of the injected dose by 15 min, and by 24 h the radioactivity in all tissues except muscle was significantly below that found in either the low CEA group or in mice without tumours. No difference in radio-antibody clearance pattern was found between mice without tumours and the group with low levels of serum CEA. In spite of higher levels of CEA within the tumour in mice with elevated serum CEA, the rapid clearance of antigen-antibody complexes reduced tumour localisation to one quarter of that seen in mice with low serum, and correspondingly low tumour, CEA levels. Gamma-camera imaging confirmed these results. Possible implications to patient selection and treatment are discussed.