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Biomedical subjects

E Bombardieri

Publications and source records attributed to E Bombardieri.

At least 91 records · Page 5Linked to original sources

How alternative are immunoassay systems employing non-radioisotopic labels? A comparative appraisal of their main analytical characteristics.

The immunoassay is one of the most sensitive and reliable analytical techniques available in the clinical laboratory. The original label for immunoassays was radioisotopes, and these methods, radioimmunoassay (RIA) and immunoradiometric assay (IRMA) are still the reference methods, because of invulnerability of the radioactive emission with respect to environmental interference. Labels other than radioisotopes have been tested for use in immunoassay to improve the sensitivity and reliability and to avoid some of the disadvantages of radioisotopic techniques. New labels have continued to be developed (Horseradish peroxidase-HPR-, pyrophosphatase, luciferases, pyrodopirazines, europium cryptates, porphirins, phosphors) and new label detection methods have been set up (e.g. chemiluminescence assay, thermometric assay, NADP+ and FADP- based coupled assay). New immunoassay strategies such as simultaneous multianalyte automated test have been developed and the reliability of the assays has in some cases caused division among researchers about the choice between the radioisotopic immunoassay or the non-radioisotopic immunoassay, as considerable effort and investment had been devoted to the search for more sensitive and practicable tests than the classic RIA-IRMA methods. The evolution of immunoassays (Monoclonal Antibodies, non-radioactive tracers, automation) has produced systems which allow a large number of laboratories to determine a great number of analytes with very good practicability. The availability of fully automated systems has generated the opinion that analytical performance of immunoassays can be considered similar to that of many traditional parameters of clinical chemistry. This conclusion seems however too optimistic, in fact data collected from interlaboratory studies demonstrate that problems concerning the analytical reliability of the measurements still remain not completely solved. In the authors' opinion, this opposition between immunological assay based on isotopic or non-isotopic labels is misleading, because each assay (whether it uses isotopic, enzymatic, fluorimetric or luminescent labels) has its own analytical characteristics and performance. For this reason the term "alternative", used to indicate all non-isotopic assays as a unique class of tests, should be abandoned. From a theoretical point of view the choice should not be between isotopic and non isotopic techniques. For each analyte to be tested, it is advisable to use the immunological assay that suits the requirements of the laboratory, irrespective of type of label. From a practical point of view, the choice should be based on the analytical performance and on the characteristics of each assay, on its cost and the type of instrumentation available in the laboratory, and on the experience and the knowledge of the laboratory personnel.

Costs and Cost Analysis↗

111In-DTPA-D-Phe-1-octreotide scintigraphy of small cell lung cancer.

Twenty-one patients with small cell lung cancer (SCLC) were investigated with 111in-octreotide (111-In-OCT) scintigraphs, 5 hours after the i.v. injection of 111 MBq of the radiotracer. Whole-body and planar scintigraphy as well as SPECT of the thorax were required. The scintigraphic results were compared to those of other conventional diagnostic procedures used for the staging and follow-up of SCLC patients. 111In-OCT detected 86% (48/56) of the lesions already known at the time of scintigraphy, being positive for all 20 SCLC lesions and negative for one lung adenocarcinoma. 111In-OCT showed a high sensitivity for mediastinal metastases (94%) and good sensitivity for bone (75%) and abdominal lymph node metastases (71%). It did not detect 2 liver metastases but revealed 5 unknown lesions which were then confirmed by other diagnostic examinations. 111In-OCT was also effective in patients with low levels of NSE. Three patients received cold octreotide for seven days to investigate whether this treatment might affect SCLC imaging. Scans were performed before and after treatment. The 111In-OCT uptake increased in the cancer lesions while the fixation in normal tissues decreased, demonstrating enhancement of SCLC imaging following cold octreotide administration.

Adenocarcinoma↗

Cytokeratin 19 fragment CYFRA 21-1 compared with carcinoembryonic antigen, squamous cell carcinoma antigen and neuron-specific enolase in lung cancer. Results of an international multicentre study.

The diagnostic value of the water-soluble cytokeratin 19 fragment CYFRA 21-1 in lung cancer was assessed in comparison with carcinoembryonic antigen, squamous cell carcinoma antigen, and neuron-specific enolase. The cut-off value, defined as 95% specificity versus a group of 526 patients suffering from benign chest diseases, was set at 3.3 micrograms/l for cytokeratin 19 fragment CYFRA 21-1 (carcinoembryonic antigen: 7.8 micrograms/l, squamous cell carcinoma antigen: 1.9 micrograms/l, neuron-specific enolase: 13.7 micrograms/l). Elevated pretreatment cytokeratin 19 fragment CYFRA 21-1 concentrations were recorded: in 112 of 244 (46%) patients with all histological types of lung cancer (carcinoembryonic antigen: 32%, squamous cell carcinoma antigen: 25%, neuron-specific enolase: 28%), in 89 of 177 (50%) patients with non-small cell lung cancer (carcinoembryonic antigen: 33%, squamous cell carcinoma antigen: 24%, neuron-specific enolase: 12%), in 47 of 81 (58%) patients with squamous cell carcinoma (carcinoembryonic antigen: 23%, squamous cell carcinoma antigen: 32%, neuron-specific enolase: 14%), in 27 of 63 (42%) patients with adenocarcinoma (carcinoembryonic antigen: 44%, squamous cell carcinoma antigen: 14%, neuron-specific enolase: 9%), in 15 of 33 (45%) patients with other non-small cell lung cancer (carcinoembryonic antigen: 36%, squamous cell carcinoma antigen: 24%, neuron-specific enolase: 14%), and in 20 of 55 (36%) patients with small cell lung cancer (carcinoembryonic antigen: 32%, neuron-specific enolase: 77%). Three of 12 patients with undefined histological type showed cytokeratin 19 fragment CYFRA 21-1 elevations. The best performance in terms of sensitivity and diagnostic accuracy was attained with the cytokeratin 19 fragment CYFRA 21-1 test in squamous cell carcinoma. In small cell lung cancer neuron-specific enolase was confirmed to be superior to the other markers. Cytokeratin 19 fragment CYFRA 21-1 concentrations increased with the extent of the malignant disease in non-small cell lung cancer. The positivity rate of cytokeratin 19 fragment CYFRA 21-1 in tumour stage TNM I was only 23% (carcinoembryonic antigen: 23%, squamous cell carcinoma antigen: 14%), i.e. the markers under study cannot be used for the diagnosis of early stage disease. Cytokeratin 19 fragment CYFRA 21-1 differentiated significantly between squamous cell carcinoma and the other histological types (p < 0.01). In addition, cytokeratin 19 fragment CYFRA 21-1 distinguished significantly the operable group TNM I-IIIa from inoperable TNM IIIb-IV (p < 0.05), but not TNM IIIa from IIIb. Out of 177 patients with non-small cell lung cancer, 90 individuals were monitored after surgery.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗

111In-octreotide uptake in granulomatous and tumor lesions in a patient with small-cell lung cancer.

A case of a patient with small cell lung cancer and right submandibular node enlargement due to granulomatous lymphadenitis is presented. Diagnostic procedures included: biopsy of the cervical node, transmission computed tomography of the chest, bronchoscopic examination and biopsy of the pulmonary lesion. The patient underwent 111In-octreotide scintigraphy (whole body and single photon emission tomography) which revealed both lesions. We conclude that granulomatous lesions are to be considered as a possible cause of false positive results, when octreotide scintigraphy is used to evaluate distant metastases in patients with known cancer.

Carcinoma, Small Cell↗

Bone scintigraphy in breast cancer: a ten-year follow-up study.

Two-hundred and sixty patients with T2-T3a, pN1, M0 (TNM classification) breast cancer underwent clinical and instrumental follow-up (mean 122 months) including periodic bone scintigraphy. A total of 1971 scintigraphic examinations were performed (range 3 to 15 scintigraphies/patient, mean 8). The results of scintigraphy were compared to standard radiographs and to the clinical history of the patients. Bone metastases occurred in 71% of 122 patients who suffered from tumor recurrence during the study. Bone lesions (alone or associated with other tumor lesions) represented the most common site (42%) of first tumor relapse and occurred as first site of distant metastases in 11% of 29 patients with locoregional relapse. Bone metastases were symptomatic in 41% of cases. The sensitivity and specificity of bone scintigraphy were 98% and 95%, respectively; the positive and negative predictive values were 73% and 100%; the accuracy was 96%. Scintigraphic false positive results occurred particularly in the skull and in the ribs and generally when the examination detected less than three focal abnormalities. This study demonstrates that the number of positive scintigraphies during follow-up increases over the years, reaching a plateau only at approximately 8-10 years. It is therefore not advisable to stop performing bone scintigraphies after the first years of follow-up as this may lead to the loss of important information.

Adult↗

Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results.

Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.

Adolescent↗

CA 15.3 determination in patients with breast cancer: clinical utility for the detection of distant metastases.

In 81 healthy women, 26 pregnant women, 25 patients with fibrocystic disease and 144 breast cancer patients, the overall diagnostic sensitivity and specificity of the CA 15.3 test was 27 and 97%, respectively. The positive and negative predictive values were 93 and 43%. In 150 node-negative patients taking part in a chemoprevention trial CA 15.3 was assayed at baseline and every 4 months for a median follow-up of 24 months (range 4-48). In these patients, 5 had local recurrences, 1 had a regional recurrence, 9 had distant metastases and 3 developed cancer in the contralateral breast. Among the patients with recurrences, those with distant metastases showed the highest ratio of CA 15.3 increase (8/9); in local and regional recurrences, this ratio was lower (2/6). The patients with contralateral breast cancer had no significant increase in CA 15.3. Patients in whom metastases were detected showed an increase in CA 15.3 4-48 months before clinical or instrumental detection of the metastases.

Adult↗

[Angiocardioscintigraphy in the cardiological surveillance of chemotherapy with anthracyclines].

Equilibrium angiocardioscintigraphy is a noninvasive nuclear medical method which allows cardiac function to be assessed. It is widely used in oncology since some clinically important drugs used in antitumor chemotherapy have a marked cardiotoxic effect. Angiocardioscintigraphy enables several parameters characteristic of cardiac function to be assessed, namely the left ventricular ejection fraction whose alterations during chemotherapy allow possible cardiotoxic side effects to be revealed before the development of irreversible heart failure.

Antibiotics, Antineoplastic↗

Evaluation of mucinous-like cancer antigen (MCA) in women with breast disease: preliminary results.

Mucinous-like cancer antigen (MCA) is a substance which is recognized by a novel monoclonal antibody, designated b12, when directed against a mixture of human breast cancer cell lines. The present study was carried out by means of a solid phase enzyme immuno assay to determine, prior to treatment, circulating levels of MCA in 131 women with malignant and in 99 with benign breast diseases (BBD). Statistical analysis did not reveal any significant difference between MCA values in healthy controls vs. BBD patients. By contrast, MCA levels were significantly higher in cancer patients as compared to the other groups (p less than 0.001). In particular, patients with metastatic disease had the highest MCA concentrations. The sensitivity and specificity of the test were 25.5 and 97.5%, respectively. The characteristics of MCA (low sensitivity, high specificity) encourage its evaluation as an indicator of tumor burden.

Adolescent↗

Clinical protocols for the application of tests for circulating tumor markers.

Circulating marker level determination in clinical practice requires an adequate strategy of application, in view of the particular features of the parameter related to the marker. The test result, which is usually expressed in terms of concentration, cannot be considered as an absolute value because every biochemical tumor indicator expresses an activity of the tumor which generally leads to increased levels of a "normal" substance in blood or biological liquids. Therefore, the result should be interpreted as a dynamic variation occurring in time, and should always be related to a previous reference value. This means that marker determination in clinical practice should be repeated periodically, both for the evaluation of tumor response to treatment and for the detection of recurrence after radical surgery. A single measurement at the time of disease presentation can characterize the tumor with regard to its capacity of producing the signal, and consequently regarding its extent and growth. These laboratory findings are of no value whatever if they are not integrated with all the other available clinical and instrumental data concerning the neoplasm; only then can they provide useful additional information. Also, all biological variables should be taken into account which may affect circulating marker levels independently of the history of the tumor such as sex, age, clearing organ function, race, alcohol and tobacco habits, concomitant diseases. These procedural protocols should be outlined and codified for each individual neoplasm since it is useless to work with scattered data which are not ordered in some kind of procedural logic.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

Neuron specific enolase (NSE) and thymidine kinase (TK) as markers in biological fluids of brain tumor patients.

We studied the activity of two enzymes NSE and TK in the biological fluids of 104 patients with nervous system diseases, who fell into 4 groups. 20 subjects out of 35 in the tumor group had glial tumors. We fixed a cut-off value of NSE and TK activity at the 95th percentile of the control group, both in serum and in CSF. The aim of our investigation was to assess the reliability of TK and NSE assays in separating brain tumors from other neurological diseases. In our patients, most of the TK activity above the cut-off value was found in the tumor group. Serum TK seems to be a useful marker for following up cerebral tumors after surgery, but NSE is less useful for this purpose.

Biomarkers, Tumor↗

Cell kinetics of hepatic metastases as a prognostic marker in patients with advanced colorectal carcinoma.

Cell kinetics was determined, as 3H-thymidine labeling index (LI), in hepatic lesions from 36 patients with primary colorectal carcinoma: LI values ranged from 0.9% to 23.5% and were normally distributed. Cell kinetics was not related to sex or age of the patient, or to liver function. For clinical studies the median LI value of 10% was used to separate slowly and rapidly proliferating lesions. Univariate analysis showed that patients radically resected and with a low LI tumor have a longer disease-free interval and a better probability of 12-month survival than those non-radically resected and with a high LI tumor. When treatment and cell kinetics were taken into consideration, the probability of 12-month survival was 100% for patients with slowly proliferating and radically resected hepatic metastases. Patients with rapidly proliferating tumors, regardless of type of treatment, had the worst prognosis.

Adenocarcinoma↗

A mucinous-like carcinoma-associated antigen (MCA) in the tissue and blood of patients with primary breast cancer.

The monoclonal antibody (MAb) b12 raised against human breast cancer cell lines was found to identify an epitope of a mucinous-like carcinoma associated antigen (MCA) that is strongly represented on breast tumor cells. The b12 MAb was used to develop an enzyme immunoassay (EIA) kit. MCA levels were measured with the EIA method in the cytosol of both breast cancer and normal breast tissue as well as in the blood of 147 patients with primary breast cancer and 92 healthy subjects. MCA cytosol levels were significantly higher in carcinoma than in normal breast tissue cytosol samples. Higher MCA levels were found in the cytosol of tumor without lymph nodal involvement. The 95th percentile of the MCA value distribution in the healthy control group (11.0 U/ml) was chosen as negative/positive cut-off level. The overall positivity rate in breast cancer group was 26.5% with MCA showing a trend toward higher levels in patients with more advanced disease. Significantly higher levels were found in patients with a higher number of positive lymph nodes.

Adult↗

Plasma and tissue CEA and TPA markers in operable breast cancer. Preliminary results.

CEA and TPA were studied in sera and in histologic specimens of 200 patients with benign (77) or malignant (123) breast pathology. The frequency and expression of the two markers was different in benign and in cancer tissues. Histologic positivity and high levels of circulating markers were observed more frequently in cancer patients than in patients with benign disease. Tissue positivity for the two tumor markers did not always correlate with elevated levels of circulating markers. Positive CEA and TPA incidence was higher in tissue samples than in serum samples. In the breast cancer group, among 33 patients with histologic positivity for CEA, only 5 cases had circulating CEA levels higher than 5 ng/ml; among 91 patients with histologic positivity for TPA, only 45 cases showed circulating levels for TPA higher than 95 U/l. These findings confirm that tumor size, secretory characteristics and vascular supply are factors affecting the achievement of high circulating marker levels. Combined marker measurement in serum and tissues can provide more information about the presence of a given tumor marker. A limited evaluation of the prognostic meaning of the study of combined CEA and TPA in sera and in tissues was carried out during the follow-up of 60 evaluable patients. Only 5 patients had cancer relapses in the first 12 months from surgery; in 2 of 5 patients TPA was positive initially and at the time of recurrence, in serum as well as in tissues. Circulating CEA gave negative findings in all relapsed patients; 2 of them showed weak positivity only in the histologic staining at the time of presentation.

Adult↗

Immunoscintigraphy of colorectal carcinoma with F (ab')2 fragments of anti-CEA monoclonal antibody.

A monoclonal antibody to carcinoembryonic antigen (CEA) (F023C5), belonging to IgG1 class, was obtained by cell fusion technique. Preliminary screening on different tissues was performed with immunoperoxidase staining, which showed good specificity of the antibody for gastric and colorectal carcinomas. F(ab')2 fragments were subsequently prepared and labeled with 131I and 111In. After immunoreactivity check the radiopharmaceuticals were injected intravenously. Sixteen patients with 22 primary or secondary localizations of colorectal carcinoma were studied following the recommendations of the ethical Committee of the Istituto Nazionale Tumori, Milan, Italy. Serial scans were performed after injection of the two radioactive reagents. In vivo pharmacokinetics of the compound was studied. Radioactivity level in surgical specimens was measured, and immunostaining was performed. All tumors were found to express the antigen. Eleven out of 12 tumor localizations of the gastrointestinal tract and three out of ten liver metastases were imaged. Specificity of tumor uptake was assessed by simultaneous injection of an irrelevant antibody.

Antibodies, Monoclonal↗

Orchiectomy alone in clinical stage I nonseminomatous testis cancer: a critical appraisal.

Sixty-two consecutive patients with clinical stage I nonseminomatous testicular cancer were entered into a prospective study to receive no treatment after orchiectomy until clinical evidence of recurrent disease. Of 59 evaluable cases, 41 (69.5%) remained continuously disease free for a median duration of 30 months (range, 18 to 46 months), and evidence of metastatic disease developed in 18 patients (30.5%) from 2 to 36 months after orchiectomy. The median disease-free interval for relapsing patients was 6 months. Retroperitoneal metastases developed in ten patients; seven patients had pulmonary metastases, and one patient had progressive elevation of the serum alpha-fetoprotein level. Relapses were significantly more frequent in patients with either embryonal carcinoma, infiltrating testicular cancer (pT greater than 1), peritumoral vascular invasion, or in those who underwent transscrotal biopsy. One patient with relapse refused salvage therapy and died. The remaining 17 patients have been rendered disease free with cisplatin combination chemotherapy and/or surgery. However, two patients showed further recurrence, with one in the lung and the other one also in the retroperitoneal nodes. In our opinion, surveillance following orchiectomy will provide useful information in clinical stage I nonseminomatous testicular cancer, but it is a difficult study. For the time being, it should be restricted to specialized centers only. In the meanwhile, retroperitoneal lymphadenectomy remains the standard treatment.

Adolescent↗