Serum and tissue CEA in colorectal cancer: clinical relevance

PURPOSE: This article is an analysis of the information derived from the determination of tumor-tissue concentration of CEA in patients with colorectal cancer. To ascertain the relationship between tumor marker content with the histologic aspects and serologic levels of CEA of this neoplam. MATERIALS AND METHODS: 136 patients with colorectal adenocarcinoma and 41 with colorectal benign processes are analyzed and followed during an average time of 27 months. The CEA of the serum were obtained preoperatively and postoperatively and measured by radioimmunoassay (RIA). Tissular CEA levels were determined with RIA. The histological characteristics are analyzed (Dukes classification, grade of differentiation, index of atypia, microscopic vascular and lymphatic involvement. RESULTS: 1) The cut off point of the tissular CEA with the best sensitivity and specificity for the diagnosis of normal mucosa is 386 ng/mg and for tumoral tissue is 1160 ng/mg. 2) There is no correlation between tissue and serologic CEA value. 3) The tissular level of CEA have a significant statistical correlation with Dukes stage (p < 0.003); other histological characteristics were no significative. 4) There are significant statistical correlations between serologic CEA and relapse but no with survival rates. CONCLUSIONS: 1) Serologic CEA levels depend on numerous factors. 2) There aren't correlations between preoperative serologic levels and tissular CEA levels. 3) Tissular CEA do not predict what patients will have an elevated serologic CEA level in relapse.     

A comparative analysis of the serum levels of NCC-ST-439, CEA and CA19-9 in patients with colorectal carcinoma

To investigate the usefulness of NCC-ST-439 (ST439) as a new tumor marker in colorectal cancer, we compared its serum level with the serum levels of CEA and CA19-9. The serum levels of ST439, CEA and CA19-9 from 168 patients were evaluated, of which 124 were primary cases and 44 were recurrent. ST439 was elevated in 31.5% in primary cases and 52.3% in newly-discovered carcinoma patients with confirmed recurrent cases. Following resection of the tumor, ST439 levels decreased rapidly. Similar trends in serial CEA and CA19-9 levels were found. While CEA is more sensitive for the detection of colorectal carcinomas than the other two markers, ST439 is sensitive in the detection of localized carcinomas and recurrent cases with localized lesions or liver metastasis. The results indicate that ST439 is a useful tumor marker not only for diagnosing primary carcinomas, but also for the detection of recurrent cases.     

Prognostic factors in colorectal adenocarcinoma

Aim of this study was to analyse prognostic factors of improved survival after resection of colorectal cancer. We studied 715 patients by retrospective review operated for colorectal adenocarcinoma. Survival was analyzed by the Kaplan-Maier method. Comparisons were made by log rank analysis. The overall survival is 75% at 1 years, 41.0% at 5 years, 29.7% at 10 years. A significant difference was noted in the survival rate according to age of the patients (p < 0.01), preoperative serum level of carcinoembryonic antigen (CEA) (p < 0.05), the performance status (p < 0.05), intestinal obstruction (p < 0.01), clinicopathological stage of the tumour (p < 0.05). Other factors including the sex, the clinical diagnosis of anaemia, the site of the tumour and histological grade had no apparent influence on survival. To define high-risk groups of recurrence is important for adjuvant therapy and follow-up study.     

Preoperative CEA level: a prognostic test in patients with colorectal carcinoma

Preoperative and postoperative carcinoembryonic antigen (CEA) levels were evaluated in 42 patients with colorectal carcinoma. Preoperative CEA values correlated inversely with survival at a statistically significant level and provided prognostic information not available by pathologic staging. Postoperative plasma CEA can accurately predict recurrent disease and may, when serial values are elevated, serve as an indication for a second-look procedure.     

Less common metastases of colorectal adenocarcinoma

The authors present an account on four patients, treated because of colorectal carcinoma who had solitary secondaries of a colorectal tumour at less common sites. Twice a secondary in the urinary bladder wall was found once in the right cerebral hemisphere and once in the humerus.     

Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis

We have developed a real-time quantitative PCR assay to measure the concentration of fetal DNA in maternal plasma and serum. Our results show that fetal DNA is present in high concentrations in maternal plasma, reaching a mean of 25.4 genome equivalents/ml (range 3.3-69. 4) in early pregnancy and 292.2 genome equivalents/ml (range 76. 9-769) in late pregnancy. These concentrations correspond to 3.4% (range 0.39%-11.9%) and 6.2% (range 2.33%-11.4%) of the total plasma DNA in early and late pregnancy, respectively. Sequential follow-up study of women who conceived by in vitro fertilization shows that fetal DNA can be detected in maternal serum as early as the 7th wk of gestation and that it then increases in concentration as pregnancy progresses. These data suggest that fetal DNA can be readily detected in maternal plasma and serum and may be a valuable source of material for noninvasive prenatal diagnosis.     

Carcinoembryonic antigen (CEA) assays in obstructive colorectal cancer

Four of 40 patients with resectable colon or rectal cancer had tumors causing acute large bowel obstruction with colonic dilatation; all 4 patients had preoperative CEA titers above 10 ng/ml with a mean of 28 ng/ml. Thirty-six cancer patients without acute colon obstruction had a mean CEA titer of 4.5 ng/ml; only 6 of 36 patients had circulating CEA titers 10 ng/ml or greater. This suggested that pre-treatment CEA titers in patients with obstructing cancer are unusually high. Multiple CEA assays were performed on two of the 4 patients with colonic obstruction before and after bowel decompressive procedures and prior to their definitive treatment. Relief of obstruction alone produces marked reduction in circulating CEA; this suggested that not only the extent of disease but also the pathophysiological changes associated with obstruction influenced circulating CEA levels.     

Cytogenetic analysis of 52 colorectal carcinomas--non-random aberration pattern and correlation with pathologic parameters

Cytogenetic analysis of short-term cultures from 52 colorectal carcinomas revealed a normal karyotype in 13 and clonal chromosome aberrations in 39 tumors. In the abnormal group, 13 tumors had simple numerical changes only, whereas 26 had at least one structural rearrangement with or without concomitant numerical changes. The most common numerical abnormalities were, in order of decreasing frequency, +7, -18, -Y, +8, +13 and -14. The most common structural rearrangements affected, again in order of decreasing frequency, chromosomes 8, 1, 6, 7, 17, 3, 11, 13, 14, 16, 2 and 10. The chromosome bands most frequently involved in the structural changes were 8q10, 17p11, 11q13, 8p11, 6q21, 7p15, 7q36, 12q13, 13q10, and 16q13. The most frequent genomic imbalances brought about by the structural rearrangements were losses from chromosome arms 8p, 1p, 6q, 17p, 7p, and 16q, as well as gains of 7q, 8q, 13q, and 11q. A statistically significant (p < 0.05) correlation between the karyotypic pattern and tumor grade was found, with the poorly differentiated carcinomas generally having more massive chromosomal abnormalities.     

The CEA test and other immunological tests as disease course controls in gastrointestinal adenocarcinoma

161 patients with adenocarcinoma of the gastrointestinal tract were studied to determine the value of the CEA test and a battery of non-specific immunological tests during the course of the disease. The ability of these tests to detect a tumor recurrence in radically operated patients was evaluated. A false negative preoperative CEA value was found in 40% of the patients with gastric carcinoma and 32% with colorectal carcinoma. Patients with a negative preoperative CEA value, and those with only slightly elevated values, had a distinctly better prognosis regarding initial operability and tendency to postoperative recurrence than patients with primarily markedly elevated values. With few exceptions, the development of distant metastases was detected earlier and more easily with the CEA test than by the usual routine follow-up methods. However, in the event of isolated local recurrence the CEA test was positive in only 1 of 5 patients. This reflects the direct correlation between tumor size and CEA elevation. The CEA test is a valuable supplement in the follow-up of patients with gastrointestinal carcinoma.     

Quantitative analysis of serum neutralization of human immunodeficiency virus type 1 from subtypes A, B, C, D, E, F, and I: lack of direct correlation between neutralization serotypes and genetic subtypes and evidence for prevalent serum-dependent infectivity enhancement

Human immunodeficiency virus type 1 (HIV-1) M group strains have been assigned to date to nine distinct genetic subtypes, designated A through I, according to phylogenetic analyses of nucleotide sequences of their env or gag genes. Whether there is any relationship between phylogenetic subtypes and the neutralization serotypes is not clear, yet defining the nature of any such relationship by mathematical means would be of major importance for the development of globally effective HIV-1 vaccines. We have therefore developed a quantitative method to analyze serum neutralization of HIV-1 isolates and to identify HIV-1 neutralization serotypes. This method involves calculations of the neutralization index, N(i), a newly defined parameter derived from plots generated from in vitro neutralization assays, calculations of pairwise serum-virus vector distances, and cluster analyses. We have applied this approach to analyze three independent neutralization matrices involving primary HIV-1 strains and sera from genetic subtypes A, B, C, D, E, F, and I. Detailed serum and HIV-1 isolate cluster analyses have shown that in general, the identified neutralization serotypes do not directly correlate with HIV-1 genetic subtypes. These results suggest that neutralization serotypes do not during natural HIV-1 infection are not governed by antibodies directed against simple epitopes within gp120 monomers. A significant proportion (28%) of 1,213 combinations of sera and HIV-1 isolates caused serum-dependent infectivity enhancement [negative N(i) values] rather than neutralization. We also noted that negative N(i) values tended to correlate better with certain HIV-1 isolates rather than with HIV-1-positive sera. Syncytium-inducing variants of HIV-1 were slightly more likely than non-syncytium-inducing variants to undergo serum-dependent infectivity enhancement, although the latter variants could clearly be susceptible to enhancement.     

Patterns of serial CEA assays and their clinical use in management of colorectal cancer

Through persistent clinical research efforts, the CEA test has developed into a useful although complex disease monitor for colorectal cancer. Although improved or prolonged survival from its use has not been demonstrated, CEA monitoring may allow more knowledgeable patient management. Several reports indicate that postoperative serial CEA assays may identify patients with early recurrence, especially when assays are done frequently. Patients with elevated pretreatment CEA levels usually showed progressively rising titers before other objective evidence of recurrence was apparent. A progressively rising CEA titer correlated well with recurrent cancer, but a normal CEA could not be used as proof of its absence. Persistently elevated CEA titers post-treatment was caused either by persistent disease or by nontumor-related factors. The CEA assay was not a substitute for clinical follow-up but was an adjunct in the diagnosis of eary recurrence. Patients with elevated CEA levels caused by localized disease treated by radiation therapy demonstrated a marked fall in serial CEA levels if all CEA-producing tumor was localized within the radiation portal. The use of pretreatment CEA values plus the pattern of CEA reponse to irradiation may help in the selection of fulguration versus abdominoperineal resection as primary treatment for rectal cancer. Persistently low serial CEA titers after irradiation therapy correlated with disease control. The use of frequent serial CEA assays in patients treated with chemotherapy compared well with other parameters as a monitor of disease progression or regression. When used with other clinical parameters, serial CEA trends appeared to be a useful adjunct in assessing the effectiveness of chemotherapy. A fall in circulating CEA or the stabilization of a rising titer after starting chemotherapy usually indicated an effective regimen, whereas a rising CEA titer may signal may signal the need to initiate or to change chemotherapy.     

Factors influencing incidence and extension of metachronous liver metastases of colorectal adenocarcinoma. A multivariate analysis

BACKGROUND/AIM: Three hundred and eighty-seven patients surgically treated for colorectal adenocarcinoma were assessed by a multivariate analysis and the factors influencing incidence and extension of metachronous liver metastases studied. METHODOLOGY: A series of 387 patients which had been surgically treated for colorectal adenocarcinoma between January 1980 to December 1990 and followed-up over a minimum of a 5-year period was retrospectively studied. RESULTS: The most reliable prognostic markers are represented by tumor site (p < 0.05) and, more specifically, by wall infiltration (p < 0.01) and metastatic lymph-nodes (p < 0.05). The only independent variable with a significant impact on stage of metachronous liver metastases was proved to be the depth of wall infiltration (p < 0.05). CONCLUSION: This study confirms the reliability of some indicators of primary tumor in influencing incidence, but not extension, of metachronous liver metastases and this is the main problem when it comes to using prognostic factors in order to modulate the intervals of postoperative follow-up according to risk category.     

Quantitative analysis of species identification tests of bloodstains using anti-human serum

Immunological reactions of bloodstains of human and animals to anti-human serum were analysed quantitatively to determine which technique is the most effective to differentiate human bloodstains from those of animals. The lower threshold of counter-electrophoresis was 10-25 micrograms protein/ml and increased only slightly with increasing age of the bloodstains, while that of the ring test and immunodiffusion decreased greatly. In counter-electrophoresis, absorption of anti-human serum by Japanese monkey serum resulted in a marked decrease in the cross reaction with animals, and still showed no change in the lower threshold for human samples. The present results show that counter-electrophoresis is especially useful for the identification of human bloodstains.     

Quantitative radiographic follow-up of apical surgery: a radiometric and histologic correlation

BACKGROUND: Morphological changes in the corneal surface after PRK may result not only in refraction fluctuations and reduction in visual acuity, but also in changes of contrast sensitivity. The aim of this study was to investigate whether PRK has an influence on contrast sensitivity with and without glare with a subsequent effect on the ability to drive cars. PATIENTS AND METHODS: Anonymous inquiries were made by means of a questionnaire sent to 114 patients after bilateral PRK in which the patients were asked to assess subjectly their driving ability. Additionally, in 66 eyes of 66 patients with a mean myopia of -5.3 D, an investigation on contrast sensitivity was performed according to the recommendations of the DOG (German Ophthalmological Society) using a Rodenstock nyctometer. RESULTS: Postoperatively, 55% of the patients felt more comfortable driving a car than preoperatively, 31% did not recognize any change, and 14% felt more uncomfortable driving car. Contrast sensitivity with or without glare 2 weeks postoperatively was so much reduced in 77% or 53%, respectively, of the patients that the criteria for driving a car in Germany were not fulfilled. Within the first 12 months after PRK the number of impaired patients diminished but even 1 year after PRK the number of patients with reduced contrast sensitivity with and without glare was higher than before PRK. Surprisingly, however, the criteria for driving a car with respect to contrast sensitivity with and without glare were not fulfilled even before PRK by as much as 44% and 24% of the patients, respectively. CONCLUSIONS: All patients must be in formed about the possible impairment for driving a car before PRK is performed.     

Radioimmunodetection of colorectal cancer, using anti-CEA monoclonal antibody CEA102: experience of 20 cases

Verapamil and dimethylcurine are Ca2+ entry blockers of essentially different chemical structures which presumably bind to the same arylalkylamine receptor of the L-type Ca channel. A systematic conformational analysis of methoxyverapamil (D-600) and dimethylcurine has been carried out using a molecular mechanics method. The lowest minimum-energy conformations of D-600 are predisposed to chelate Ca2+ by four oxygen atoms of the stacked methoxyphenyl moieties. Comparison of the lowest energy conformations of D-600-Ca2+ and dimethylcurine revealed a similar spatial disposition of cationic groups and methoxyphenyl moieties in the two compounds. A three-dimensional model of arylalkylamine receptor was suggested which incorporates two nucleophilic areas of the Ca channel. Dimethylcurine binds to these areas by its quaternary amine functions, whereas D-600 does so by amine function and via coordinated Ca2+. The results support the hypotheses on ternary complex formation between the ligands of Ca channel, their receptors, and Ca2+.