Evaluation of CA 15-3 serum levels in breast cancer patients

A case of opacity in the fetal gallbladder was diagnosed by ultrasound. The lesion resolved spontaneously in the postnatal period. Careful follow-up ultrasound examinations are necessary for fetal cholelithiasis in the pre- and postnatal periods, and conservative management is mandatory.     

Prognostic value in predicting overall survival of two mucinous markers: CA 15-3 and CA 125 in breast cancer patients at first relapse of disease

The role of circulating tumour markers in providing prognostic information has been scarcely studied. We evaluated the prognostic significance of two mucinous markers: CA 15-3 and CA 125 in 115 breast cancer patients at first recurrence of disease. At diagnosis of advanced disease bone involvement was found in 64 patients, lung in 57, skin lymph nodes in 21, liver in 20, and brain in 5. Patients were recruited and treated in the same institution with conventional chemo- or endocrine therapy. The follow-up ranged from 3 to 54+ months (median 35). Serum samples were drawn at first recurrence of disease before the start of any endocrine and/or chemotherapy. Patients with CA 15-3 < 30 U/ml survived significantly longer than those with CA 15-3 > 30 U/ml (median 50+ versus 26 months, P < 0.02). Similarly, overall survival of patients with CA 125 < 35 U/ml was significantly higher in comparison with patients with CA 125 > 35 U/ml (median 34.5 versus 18.5 months, P < 0.001). CA 125, but not CA 15-3, maintained its prognostic value in the subgroup of patients with visceral metastases. Both markers were found to be independent prognostic variables in multivariate analysis according to Cox's model. CA 15-3 and CA 125 appeared to be powerful prognostic indicators, in addition to visceral metastases, in patients with advanced breast cancer.     

Influence of neoadjuvant chemotherapy on serum tumor markers CA 15-3, MCA, CEA, TPS and TPA in breast cancer patients with operable disease

The mycelial mass of the fungus Polyporus Squamosus strain 64 (PS-64) was disintegrated by mechanical and ultrasound treatments. After centrifugation, the supernatant containing the disintegrate was dialyzed and lyophilized. The resultant PS-64 extract was subsequently investigated as an immunomodulator of IgE and IgG responses to ovalbumin (OA) in (CBAxC57BL/6)F1 mice using passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA), respectively. Multiple injections of PS-64 extract in doses of 1.5, 15, and 150 mg/kg administered before the primary or secondary immunization of mice with OA resulted in a dose-dependent inhibition of both IgE and IgG antibody responses to OA. In contrast to the inhibition of the anti-OA IgE response noted during the entire 3-week observation period, the anti-OA IgG response was restored to control level by the third week of secondary immunization. The glass microfiber-based whole blood histamine release assay demonstrated that various concentrations of the PS-64 extract did not influence histamine release induced either by anti-IgE or by specific allergens from basophils derived from whole blood of allergen-sensitized patients. Using the hemolytic plaque assay, significant suppression of IgM-secreting cell formation was noted in (CBAxC57BL/6)F1 mice administered various doses of the PS-64 extract before immunization. The PS-64 extract inhibited the in vitro proliferation of human mononuclear cells upon stimulation with phytohemagglutinin (PHA). In a dose-dependent manner, the PS-64 extract also inhibited delayed-type hypersensitivity reaction and skin graft rejection, similar to the effect noted with usage of Cyclosporin A (CsA) in (CBAxC57BL/6)F1 mice. Our investigation suggests that the immunomodulatory effects of PS-64 should be studied further for potential clinical therapeutic utility.     

CA 15-3 and bone scintigraphy in the follow-up of breast cancer

Twenty nine patients with blunt liver trauma were recorded in the Central Hospital of Yaounde between 1986 and 1996. The average age was 23.4 years, with the 20 to 25 and 5 to 15 age groups being the most affected. The most characteristical clinical presentation was hemoperitoneum with shock. Twenty-three patients were operated (18 in emergency and 5 secondary). While 6 patients benefited from non operative treatment due to their stable hemodynamic state. Exploration of lesions revealed 16 grade I and grade II, 8 grade III and 5 grade IV and V lesions. The operation was a simple suture in 13 cases, selective ligature of hepatic artery in 2 cases and 2 tamponades while in 4 cases the treatment was inactive. The bleeding could not be controlled in 2 cases. Peri-operative mortality was 17.39% and morbidity 21.74%, made up mainly of parietal sepsis. In our practice, blunt liver trauma are generally benign and treatment should be conservative.     

Preoperative CA 15-3 concentrations predict outcome of patients with breast carcinoma

BACKGROUND: CA 15-3 is a breast-associated mucin that is elevated in the majority of breast carcinoma patients with distant metastases. Currently, the main application of this marker is in monitoring and detecting recurrences in patients with diagnosed breast carcinoma. METHODS: Preoperative serum concentrations (prior to excision of the primary tumor) of CA 15-3 were measured in 368 patients undergoing potentially curative surgical treatment for early breast carcinoma. These results were compared with prospectively recorded clinicopathologic characteristics and patient outcome data. RESULTS: A weak but significant positive association was found between CA 15-3 concentrations and both tumor stage and the number of involved axillary lymph nodes but not between CA 15-3 concentrations and estrogen receptor status. Patients with high concentrations of CA 15-3 had a significantly worse prognosis than patients with low concentrations. Using an optimum cutoff value of 30.38 U/mL, the probability of disease free survival at 5 years was 44% in patients with high CA 15-3 levels compared with 65% in patients with low CA 15-3 levels (P = 0.002, Mantel-Cox log rank test). The corresponding probabilities for overall survival were 67% and 83%, respectively (P < 0.001). The association of preoperative CA 15-3 levels with outcome was maintained in multivariate survival analysis and was not explained by the association between CA 15-3 and tumor size or lymph node burden. The relation between CA 15-3 and outcome also was found within some patient subgroups identified by traditional prognostic factors (axillary lymph node positive patients, patients with primary tumors >2 cm in greatest dimension, and patients with estrogen receptor positive tumors). CONCLUSIONS: Preoperative serum concentrations of CA 15-3 appear to have a significant relation to outcome in patients with early breast carcinoma and may have a role in the rational selection of patients for appropriate adjuvant treatments. To the authors' knowledge, CA 15-3 thus is one of the first circulating markers shown to be an independent prognostic indicator in patients with breast carcinoma.     

Clinical utility of CA125 levels in predicting laparoscopically confirmed salpingitis in patients with clinically diagnosed pelvic inflammatory disease

To investigate immune system function in obsessive-compulsive disorder (OCD) we measured plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) in 14 drug-free obsessive-compulsive patients and 14 matched healthy controls. No significant differences were observed between patients and controls in plasma levels of IL-1 beta and IL-6, whereas plasma levels of TNF-alpha were significantly lower (p = 0.001) in the former. Blood levels of prolactin did not differ between the two groups, whereas plasma cortisol concentrations were significantly higher in patients than in healthy subjects (p = 0.02). No significant correlation was found between immune parameters, on the one hand, and endocrine or psychopathological measures on the other. These results suggest that OCD is associated with a decreased production in TNF-alpha, but normal synthesis of IL-1 beta and IL-6.     

CEA and CA 15-3 in pleural effusion of advanced breast cancer patients: clinical relevance and diagnostic value

Serum and pleural effusion fluid were tested for CEA concentration in 83 advanced breast cancer patients, in 43 of whom CA 15-3 was also determined. All pleural effusions were clinically malignant. The sensitivity of the CEA test for the presence of pleural metastases was closer to that of the CA 15-3 test in effusion (0.59 and 0.79, respectively) than the sensitivity of CEA compared to CA 15-3 in serum (0.43 vs. 0.79). The use of two markers combined with cytology increased the diagnostic rate from 48% (cytologically positive) to 88% (cytologically positive and/or with one or both markers increased in effusion). A high diagnostic rate in cytologically negative effusions (65%), and in effusions presented as the sole metastatic involvement (100%), points to the clinical value of these two markers. Our results show that markers produced by pleural metastases may be secreted either into the effusion fluid or into serum, or both. This finding, as well as some other observations, are discussed in the present paper.     

The correlation of CA15.3 and TPS with tumor course in patients with metastatic breast cancer

Courts routinely award coverage for TMJ disorders under medical plans, despite exclusionary language and evidence that the insured failed to disclose preexisting treatment as required by the plan and neglected to attempt more conservative treatment first. Such decisions adversely affect both the health carrier and the plan participants. Various states have enacted legislation mandating coverage of TMJ; however, TMJ issues still exist and will remain a frequent topic for litigation until the judiciary recognizes that validating contract language ultimately benefits insureds as consumers and reinforces the integrity of the industry as a whole.     

Comparison of tissue polypeptide antigen (TPA) with cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) in follow-up of breast cancer

Cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) were measured in 679 sera of breast cancer patients and in 94 sera of women without breast cancer. The tumour markers were determined using immunoluminometric assays (ILMA). The assays are characterised by an inter-assay-imprecision and intra-assay-imprecision <4 %. The breast cancer patients were staged according to the TNM classification stage 0-IV (by UICC) in patient groups with a compatible prognosis. Median and range of each stage were investigated. The cut-off values (95th and 97.5th percentile of control group) of CA 15-3, CEA and TPA were determined; specificity, sensitivity, positive and negative predictive value (PV) and efficiency were investigated for these cut-off's and the receiver operating characteristic (ROC) curves were calculated. The differences between control group and stage 0-3 were shown as non-significant for CA 15-3 and CEA but significant for TPA. Significant differences were found in stage 4 for all three tumour markers. The three tumour markers did not have differences in specificity, positive and negative PV and efficiency. TPA and CA 15-3 demonstrated comparable results in sensitivity and ROC curve analyses. These results were better than those from CEA.     

Usefulness of CA 15-3 antigen determination for evaluation of response to second-line chemotherapy in patients with breast cancer: preliminary study

The aim of this study was to assess effects of second-line chemotherapy in metastatic breast cancer via determination of CA 15-3 marker. Analysis included 73 women, in whom distant metastases were diagnosed within 14-72 months (median: 43) after the completion of basic therapy. Average age of patients at primary diagnosis was 50.7 +/- 12.6 years. Dominant sites of metastases were: liver (27 patients) and lungs (24 patients). Serum CA 15-3 was examined immunoenzymatically at diagnosis of distant metastases and then after 2-4 cycles (median 4) of anthracycline-based chemotherapy. Changes of mean CA 15-3 values correlated with the UICC response criteria. There was a significant fall in mean levels of CA 15-3 after treatment in patients with complete (p < 0.004) and partial regression of metastatic lesions (p < 0.03). Stabilization and progression of the disease were associated with raise in CA 15-3 mean values, but the difference was significant only in the latter group (p < 0.02). In 31 out of 39 patients (79.5%) with regressive disease (complete and partial response) CA 15-3 levels decreased by at least 25% after treatment. Nine of 11 (81.8%) patients with stable disease had the antigen concentrations that did not vary by more than +/- 25% of the initial CA 15-3 value. CA 15-3 levels raised by at least 25% in 22 out of 23 (95.7%) cases with progressive breast cancer. Overall, CA 15-3 variations correlated with the disease status in 62 (84.9%) patients. These findings confirmed the usefulness of CA 15-3 determinations in evaluating the efficacy of second-line chemotherapy in patients with advanced breast cancer.     

Elevation of serum tumor marker CA 15.3 levels as the first manifestation of metastatic breast cancer to the cavernous sinus

We report rising tumor marker levels of CA 15.3 as the presenting manifestation of metastatic breast cancer to the cavernous sinus and orbit. A 39-year-old woman with a history of breast cancer developed increasing levels of tumor marker CA15.3. Ten months later, she developed vision loss in the right eye, diplopia, and right-sided ptosis. A magnetic resonance scan of the head showed a mass involving the right cavernous sinus and superior orbital fissure. Biopsy of the lesion showed metastatic breast cancer. She was treated with surgery and radiotherapy and did well. Ophthalmologists should be aware of the significance of increasing levels of tumor markers, such as CA 15.3, in patients with a history of breast cancer and new neuroophthalmologic signs or symptoms.     

Excessive breast self-examination among first-degree relatives of newly diagnosed breast cancer patients. High-Risk Breast Cancer Consortium

The influence of the primary antibody, the fixative, and the antigen unmasking technique on the method sensitivity of immunohistochemistry as a method for the identification of viral hemorrhagic septicemia (VHS) virus in paraffin-embedded specimens of naturally infected rainbow trout (Oncorhynchus mykiss) was examined. Fish (200-300 g) were collected during an outbreak of VHS. Parallel specimens from liver, spleen, kidney, and brain were fixed by immersion in 10% phosphate-buffered formalin, periodate-lysine-paraformaldehyde (PLP), Bouin's fluid, or absolute ethanol. Virus cultivation was also performed on parallel specimens, and the virus titer (TCID50/ml) was determined. Purified nucleocapsid protein (N-protein) of the virus was incorporated in an artificial antigen substrate polymerized bovine serum albumin), fixed as described above, and embedded in paraffin wax. Microwave unmasking was performed on formalin-, PLP-, and Bouin's fluid-fixed specimens. The presence of virus peptides in situ or N-protein in the artificial antigen substrates was visualized using an immunohistochemical method based on alkaline phosphatase or peroxidase and one polyclonal and five monoclonal polypeptide-specific antibodies. VHS virus was identified in situ in specimens with high virus titers (10(7-8) TCID50/ml) regardless of the fixative and without the need of an unmasking procedure. A pronounced masking effect was observed for the cross-linking formalin and PLP fixatives. Regardless of the primary antibodies used, there was a significantly higher epidemiologic sensitivity (the proportion of virus positive samples that tested positive by immunohistochemistry) using ethanol and Bouin's fluid compared with formalin and PLP (P < 0.05). At 10(5) TCID50/ml, the average sensitivity reached 0.5, and at > or = 10(6) TCID50/ml, sensitivity was 0.9. Unmasking procedures showed a moderate effect and did not result in significantly higher epidemiologic sensitivity (P = 0.17), There was great variation for the different monoclonal antibodies/antigens and fixatives. Sensitivity studies on antigen substrates were in accordance with results of in situ studies that showed the highest sensitivity for ethanol and Bouin's fluid. Virus cultivation was more sensitive than immunohistochemistry. This study showed that the fixative and the primary antibody both influence method sensitivity and that VHS virus antigens concealed during fixation are difficult to reexpose. Immunostaining for VHS virus should be performed with monoclonal antibodies specific for the N-protein, and tissue samples should be fixed in either ethanol or Bouin's fluid. Immunohistochemistry is specific but is less sensitive than virus cultivation. Immunostaining for VHS virus can be a valuable supplement to virus cultivation during acute outbreaks of disease.     

Quantitative spectral electroencephalography in predicting survival in patients with early Alzheimer disease

OBJECTIVE: To determine whether measures of quantitative spectral electroencephalography (EEG) can predict survival in patients with early Alzheimer disease. DESIGN: Prospective cohort study; median duration of follow-up was 4.4 years in survivors and 2.6 years in nonsurvivors. Cox proportional hazards models, with adjustment for age and sex were used to estimate relationships between EEG measures and survival. Log relative percentage values of EEG bands were used as predictors. SETTING: Outpatient university memory clinic. PARTICIPANTS: One hundred one consecutively referred patients with early probable Alzheimer disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria were studied with EEG at the time of diagnosis. The mean age of the patients was 79.2 years, which was higher than in previous EEG studies. MAIN OUTCOME MEASURE: Mortality. RESULTS: Fifty-one patients (50.5%) died during follow-up, with a median survival time in all patients of 4.1 years. The following EEG variables were significantly associated with increased risk of mortality: from parieto-occipital leads, higher theta (hazard ratio, 2.05; 95% confidence interval, 1.15-3.66; P<.05), lower alpha (hazard ratio, 0.43; 95% confidence interval, 0.25-0.76; P<.01), and lower beta (hazard ratio, 0.38; 95% confidence interval, 0.22-0.68; P<.001) activity; and from frontocentral leads, higher theta activity (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P<.05). Stepwise Cox regression analysis showed that loss of parieto-occipital beta (P<.01) and alpha (P<.05) power were independent and significant predictors of mortality. Both beta (12.6-35.4 Hz) and alpha (7.5-12.5 Hz) activity remained significantly associated with mortality after adjustment for education, dementia severity, symptom duration, level of cognitive function, presence of extrapyramidal symptoms or hallucinations, presence of vascular risk factors, and presence of leukoaraiosis or local cortical atrophy. CONCLUSIONS: Decreases of beta and alpha activity on quantitative spectral EEG are independent predictors of mortality in patients with early Alzheimer disease. In the clinical context, the use of EEG technology for prediction of survival in individual patients remains to be determined.     

Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients

It is unknown whether the addition of aspirin might increase both the efficacy and the potency of clopidogrel, a potent and selective ADP blocker. For that purpose, the efficacy of clopidogrel (1-20 mg/kg, p.o.) administered orally to rabbits alone or in combination with aspirin (0.1-10 mg/kg, p.o.) was determined in several experimental models. A potent synergistic effect of the clopidogrel/aspirin association was demonstrated with regard to collagen-induced platelet aggregation measured ex vivo. Similarly, aspirin potentiated the antithrombotic activity of clopidogrel measured with regard to experimental thrombosis induced by a silk thread or on stents placed in an arteriovenous shunt, thrombus formation following electrical stimulation of the rabbit carotid artery and with regard to 111In-labeled platelet deposition on a stent implanted in an arteriovenous shunt or on the subendothelium following air drying injury of the rabbit carotid artery. A similar potentiating effect of aspirin was obtained with regard to myointimal proliferation (restenosis) in the femoral arteries of atherosclerotic rabbits which occurred as a consequence of stent placement. The clopidogrel/aspirin combination showed only additive-type effects on bleeding time prolongation induced by ear transection in the rabbit, therefore showing that combined inhibition of cyclooxygenase and ADP's effects provide a marked enhanced antithrombotic efficacy. Such a combination may provide substantial protection against platelet aggregation leading to thrombotic occlusion at sites of endothelial injuries and coronary artery stenosis in humans.     

Suspected extragonadal germ-cell cancer syndrome presenting with an orbital mass and elevation of serum CEA, CA 19-9 and CA50 levels

Patients with extragonadal germ-cell cancer syndrome (EGCCS) represent a subgroup of patients with poorly differentiated carcinoma or adenocarcinoma of an unknown primary site for whom potentially curative therapy is available. We report the case of a young man presenting an orbital tumor and high serum levels of CEA, CA 19-9 and CA50 for whom an initial diagnosis of metastatic poorly differentiated carcinoma was made. Suspecting EGCCS, he was treated as for a germ-cell tumor. While in treatment, he underwent residual orbital mass resection, and the histologic diagnosis was embryonal carcinoma based on alpha-fetoprotein immunoperoxidase staining. We discuss the rare location at diagnosis, the impressive increase in the commonly considered gastrointestinal markers that he showed, and the potential utility of these markers for such patients.     

血浆D-二聚体水平与转移性胃癌患者生存期的关系

Objective: The principal purpose of this study was to determine the relationship between level of plasma D-dimer and survival time in metastatic gastric cancer patients. Methods: We retrospectively collected the data of plasma D-dimer in metastatic gastric cancer patients admitted in our Department (Department of Oncology, The Affiliated Changzheng Hospital, The Second Military Medical University, Shanghai, China) from October 2006 to October 2008 and analyzed the relationship between level of plasma D-dimer and survival time along with other clinicopathologic parameters. Results: A total of 82 patients were studied in our research, 52 were males and 30 females, and the mean age was 57 years. The 48 cases had a normal plasma D-dimer level (< 300 μg/L) and 34 had a high plasma D-dimer level (≥ 300 μg/L). In the normal and high plasma D-dimer level groups, the mean survival times were 10.9 (95% CI: 9.8-12.2) months and 6.8 (95% CI: 4.4-7.6) months respectively, and the difference was statistically significant. Conclusion: Metastatic gastric cancer patients with high plasma D-dimer level had significantly shorter survival time than those with normal plasma D-dimer level. Level of plasma D-dimer can be referred as a potential predictor in metastatic gastric cancer patients.     

Residual metastatic axillary lymph nodes following neoadjuvant chemotherapy predict disease-free survival in patients with locally advanced breast cancer

BACKGROUND: This study was performed to validate the prognostic significance of residual axillary lymph node metastases in patients with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy and to analyze other clinicopathologic factors that might be independent predictors of disease-free survival (DFS) in an attempt to identify patients in whom axillary dissection might be omitted. METHODS: One hundred sixty-five assessable patients with LABC were treated in a prospective trial of neoadjuvant chemotherapy utilizing four cycles of 5-fluorouracil, doxorubicin, and cyclophosphamide. Responding patients were treated with segmental mastectomy and axillary dissection or modified radical mastectomy. Patients subsequently received additional chemotherapy followed by irradiation of the breast or chest wall and draining lymphatics. The median follow-up was 35 months. RESULTS: Clinical tumor response to neoadjuvant chemotherapy (P = 0.046) and the number of residual metastatic axillary lymph nodes found at axillary dissection (P = 0.05) were the only independent predictors of DFS. Patients with a complete clinical response had a predictably excellent DFS and those with no change or progressive disease had a poor DFS. In patients with a partial response, the number of residual metastatic lymph nodes further stratified patients with respect to DFS (P = 0.006). CONCLUSIONS: Clinical response and residual metastatic axillary lymph nodes following neoadjuvant chemotherapy are important predictors of DFS. Patients with a clinically positive axilla following neoadjuvant chemotherapy should undergo axillary dissection to ensure local control. However, the benefit of axillary dissection in patients with a clinically negative axilla may be minimal if the axilla will be irradiated, and histologic staging does not affect subsequent systemic treatment. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following neoadjuvant chemotherapy is presently under way to evaluate this hypothesis.     

25-hydroxycholecalciferol serum levels in patients with Crohn's disease

In 37 patients with Crohn's disease the 25-hydroxycholecalciferol (25-HCC) serum level, serum concentration of calcium and inorganic phosphate, and the enzyme activity of alkaline phosphatase were measured. Furthermore the activity index of Crohn's disease was determined in every patient. There was no statistically significant difference of 25-HCC serum levels in these patients compared to a healthy control group. Correspondingly most patients showed normal alkaline phosphatase enzyme activity and normal serum concentration of calcium and inorganic phosphate. No correlation between 25-HCC concentration and site of inflammation or activity index was found.