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Biomedical subjects

P Stieber

Publications and source records attributed to P Stieber.

At least 37 records · Page 2Linked to original sources

The role of carcinoembryonic antigen for the detection of recurrent disease following curative resection of large-bowel cancer.

BACKGROUND AND AIMS: During recent years, a discussion about cost-effectiveness and importance of follow-up evaluation after curative resection of large-bowel cancer has developed. It is not known whether the determination of carcino-embryonic antigen (CEA) plays a crucial role in the early detection of recurrent disease. PATIENTS/METHODS: We conducted an analysis of the prospective follow-up database of 1321 patients after curative resection of colorectal cancer in our institution between 1990 and 1998 to evaluate the role of CEA in the early detection of recurrent disease. RESULTS: Of the 1321 patients included in our study, 306 developed recurrent disease following curative resection (23.2%). These patients with recurrent disease were divided into: Group I. No pre-operative CEA determination/insufficient follow-up (n=47; 15.4%). Group II. No elevation of CEA with primary cancer (n=156; 51.0%): (IIa) elevation with recurrent disease (n=62); (IIb) no elevation at any time point (n=53); and (IIc) role of CEA not completely elucidated (n=41). Thirteen patients of group II underwent curative relapse surgery (8.3%). Group III. Elevated CEA with primary cancer (n=103; 33.7%): (IlIa) no increase with recurrent disease (n=21); (IIIb) increase with other symptoms of recurrent disease (n=45); and (IIIc) increased values as an early symptom of recurrent disease (n=37). Sixteen patients of group III underwent curative relapse surgery (15.5%). In patients after relapse surgery, recurrent disease developed again after a median time of 12 months (mean 17.9+/-3.8 months). CONCLUSIONS: Our findings indicate that 2.8% of all patients (12.1% of patients with recurrent disease) who underwent curative resection of colorectal cancer profit from follow-up CEA determinations. With careful observation of CEA kinetics, 6.2% (n=82) of all patients or 26.8% of patients with recurrent disease could profit from routine follow-up CEA determinations. In 9.5% of patients with recurrent disease, curative resection of relapse was achieved and these patients remained disease free for a median time of 12 months. Regular CEA measurements remain an important part of routine patient care after curative resection of colorectal cancer.

Adult↗

Carbohydrate-deficient transferrin is not a useful marker for the detection of chronic alcohol abuse.

BACKGROUND: The role of carbohydrate-deficient transferrin (CDT) as a reliable marker for the detection of chronic alcohol abuse has been discussed controversially. METHODS: Therefore, we investigated CDT in the sera from 405 subjects with different alcohol intake. Besides healthy control subjects (n = 42), inpatients and outpatients in a department of gastroenterology (n = 325) and patients admitted to a department of otorhinolaryngology (n = 38) were studied. A total of 213 patients suffered from various forms of liver diseases, and 89 patients had liver transplantation. CDT values were determined by a double-antibody radioimmunoassay. RESULTS: In the 241 alcohol-abstinent subjects, CDT levels ranged from 3 to 90 units L-1 (median = 12); the 92 moderate drinkers (20-60 g of alcohol per day) showed values from 3 to 40 units L-1 (median = 12), and the 72 subjects with chronic alcohol abuse (> 60 g per day) revealed CDT levels from 3 to 100 units L-1 (median = 16). The diagnostic specificity for alcohol abuse was 86.8% for men (sensitivity 36.9%) and 95% for women (sensitivity 0%). CONCLUSION: Our data indicate that measurement of CDT does not reach clinical use in the detection of chronic alcohol abuse in an unselected population because of its insufficient specificity and sensitivity.

Alcoholism↗

Is free prostate-specific antigen helpful in the differential diagnosis of benign hyperplasia and cancer of the prostate?

PURPOSE: We studied the clinical relevance of the determination of free prostate-specific antigen (f-PSA) in addition to total PSA (t-PSA). METHODS: Both t-PSA and f-PSA values of frozen sera obtained pretherapeutically from 80 patients with prostate carcinoma (PC) and 171 patients with benign hyperplasia of the prostate (BPH) were analyzed by means of the Tandem-E PSA and Tandem-R f-PSA immunoassays (Hybritech, San Diego, Calif.). RESULTS: At 95% specificity, a cutoff value of 15.7 micrograms/l was obtained for t-PSA [9 patients with BPH (5%) were above this value]. For this cutoff value, we calculated a sensitivity of 50% (40 patients with PC were above this value). Using the same criteria for the ratio (Q) f-PSA:t-PSA a cutoff of 0.086 was found again at a specificity of 95%. In a second step, only patients with t-PSA values below the cutoff level of 15.7 micrograms/l were considered. Out of these patients, 6 of 156 with BPH (missing values = 6) and 11 of 40 with PC were below the above-mentioned ratio (Q = 0.086). Therefore, sensitivity was 28% for this subgroup. Considering both steps (t-PSA and Q) 51 patients with PC were detected correctly and 15 patients with BPH would have undergone biopsy unnecessarily (positive biopsy rate: 77%). CONCLUSIONS: High t-PSA levels are very good indicators for the presence of PC. There is still concern for improving the differentiation between BPH and PC, when an intermediate or low value (< or = 95% specificity) is observed. The determination of Q is only useful in this range and is helpful for the clinician's decision whether to apply or avoid biopsy.

Biomarkers, Tumor↗

Serum levels of intercellular adhesion molecule-1 in squamous cell carcinoma of the head and neck.

Soluble intercellular adhesion molecule-1 (s-ICAM-1) was measured in the sera of 131 patients with primary and 50 patients with recurrent squamous cell cancer of the head and neck (HNSCC). 30 patients with benign ear, nose and throat diseases served as controls. s-ICAM-1 levels in serum are high in patients with HNSCC, particularly in the advanced tumor stages (UICC IV). Highest levels can be measured at the time of tumor recurrence and locoregional lymph node metastases. The sensitivity (95% specificity) of s-ICAM-1 (cutoff-level: 473 ng/ml) is 4% at primary diagnosis and 12% for recurrent disease. A coefficient of correlation for s-ICAM-1 in combination with SCC, carcinoembryonic antigen and CYFRA 21-1 indicates that no correlation can be found of s-ICAM-1 compared with traditional tumor markers. Due to overlapping values in control and patient groups s-ICAM-1 is not suitable for a specific clinical use in HNSCC.

Antigens, Neoplasm↗

Clinical significance of the tumour markers CA 125 II and CA 72-4 in ovarian carcinoma.

In a retrospective study we compared the usefulness of the tumour marker CA 72-4 with the established marker CA 125 II (both EIA on Cobas-Core, Hoffmann LaRoche, Basel Switzerland) at the time of primary diagnosis of ovarian carcinoma (n = 123) in order to discriminate between ovarian carcinomas of different histological type. We compared their diagnostic value, behaviour in follow-up care and evaluated possible combinations. Fixing specificity at 95% vs. benign gynaecological diseases (n = 37) as the clinically relevant reference group, we found cut-off values of 160 U/mL for CA 125 II and 3.0 U/mL for CA 72-4. On the basis of this specificity, we found comparable sensitivity for CA 125 II and CA 72-4 for all kinds of ovarian carcinoma at the time of primary diagnosis. With regard to histology, we found best sensitivity for CA 125 II in serous ovarian cancer and for CA 72-4 in mucinous ovarian cancer. Additional sensitivities were found in ovarian carcinoma in general but little in serous ones. No additive sensitivity was found in mucinous ovarian carcinomas with CA 72-4 as leading marker. In follow-up care, CA 72-4 was the leading marker in II cases and CA 125 II in 16, while in one case both markers were negative. In 6 cases the change of values reflecting clinical follow-up-care was within the so-called reference range. According to our results, at the time of primary diagnosis because of lack of histological findings the combined determination of CA 125 II and CA 72-4 can be recommended. In follow-up care and control of efficacy of therapy the preoperative positive or leading marker is generally sufficient. The determination of both markers in follow-up care is indicated only if they both are negative at primary diagnosis and until one of them becomes clearly positive.

Adenocarcinoma, Mucinous↗

Methodological and clinical evaluation of two automated enzymatic immunoassays as compared with a radioimmunoassay for neuron-specific enolase.

We evaluated the clinical and methodological features of the neuron-specific enolase radioimmunoassay (NSE RIA) (Pharmacia = Ph) with the neuron-specific enolase enzyme immunoassay (NSE EIA) on the ES 700 (Boehringer Mannheim = BM) and the NSE EIA on the Cobas Core System (Roche = Ro). A total of 253 serum samples obtained from 37 healthy persons, 45 patients with benign lung diseases, 124 patients with lung cancer (42 with small cell lung cancer, 23 with adenocarcinoma, 21 with squamous cell carcinoma, 11 with large cell carcinoma, and 27 with unknown histology), 34 with lung metastases, 7 patients with sarcoma and 6 patients with malign lymphatic diseases were stored at -80 degrees C and assayed retrospectively. The intra- and inter-assay imprecisions were lower for the automatized test systems than for the RIA. Correlation between the EIA's and the RIA was better for NSE (Ro) than for NSE (BM) (BM/Ph: r = 0.93 and slope = 0.54; Ro/Ph: r = 0.95, slope = 0.79), but weaker than the correlation between the two EIA's: over the whole range r = 0.96, neuron-specific enolase < 50 micrograms/l: r = 0.97, neuron-specific enolase < 20 micrograms/l: r = 0.92. Fixing the specificity at 95% versus benign lung diseases we found a cut off value of 11.9 micrograms/l for NSE RIA (Ph), 15.9 micrograms/l for NSE EIA (BM) and 13.5 micrograms/l for NSE EIA (Ro). Based on this specificity of 95% versus benign lung diseases as the clinically relevant reference group, the sensitivity for NSE RIA was 32% for all lung cancer and 45% for small cell lung cancer, for NSE EIA (BM) 35% for all lung cancer and 43% for small cell lung cancer, the NSE EIA (Ro) had a sensitivity of 42% for all lung cancer and 57% for small cell lung cancer. In a follow-up study of two patients with small cell lung cancer a good comparability for all three assays in the kinetics, but a marked difference in the neuron-specific enolase value levels was found. The results show that the NSE EIA (Ro) on Cobas Core system is the most sensitive assay for the detection of small cell lung cancer.

Enzyme-Linked Immunosorbent Assay↗

Methodological and clinical comparison of the ACS prostate-specific antigen assay and the Tandem-E prostate-specific antigen assay in prostate cancer.

OBJECTIVES: The new ACS prostate-specific antigen (PSA) assay was methodologically and clinically compared with the established Tandem-E PSA assay. We intended to find a possible advantage in primary diagnosis and monitoring the recurrence of prostate cancer due to the additional better recognition of the free PSA form by the ACS PSA assay. METHODS: sera of 51 healthy men, 127 patients with hyperplasia, and 82 untreated patients with prostate cancer were analyzed by means of the Tandem-E PSA assay (Hybritech) and the ACS PSA assay (Ciba Corning). Follow-up was done on 12 cancer patients with recurrences. RESULTS: Both assays correlated very well (r = .98 for all studied men or hyperplasia patients or cancer patients). However, both assays did not yield comparable values: The ACS assay was characterized by nearly doubled values compared with the Tandem-E assay. At 95% specificity versus patients with benign hyperplasia, cutoff values were obtained as follows: 28.8 ng/mL for the ACS PSA assay and 15.2 ng/mL for the Tandem-E assay. At 95% specificity versus hyperplasia patients, we calculated sensitivities of 60% (ACS PSA) and 63% (Tandem-E PSA). Our longitudinal study revealed more prominent slopes for the ACS assay in patients with recurrent cancer disease. However, using either the ACS assay or the Tandem-E assay, the PSA increase started at the same time. In 1 patient, the increasing ACS PSA accelerated 3 months earlier than the increasing Tandem-E PSA did. CONCLUSIONS: The ACS assay has obviously higher PSA levels. The clinician is not familiar with such high PSA levels. The specificity-sensitivity profile nonetheless remains unchanged. If the PSA concentration is measured by the ACS assay, patients who relapse will reveal a more rapid PSA increase. Then, recurrent cancer disease may be detected earlier in some cases.

Adult↗

CYFRA 21-1. A new marker in lung cancer.

BACKGROUND: It is known that cytokeratin 19 is particularly abundant in carcinoma of the lung. METHODS: A sandwich enzyme-linked immunosorbent assay called CYFRA 21-1 was, therefore, developed to detect soluble cytokeratin 19 fragments in serum using two specific monoclonal antibodies (Ks 19.1 and BM 19.21). The authors investigated the clinical significance of this new marker compared with the established markers carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron-specific enolase (NSE), carbohydrate antigen (CA) 19-9, CA 125, CA 15-3, CA 72-4, alpha-fetoprotein, and prostate-specific antigen in a pilot study on 1741 serum samples from patients with various benign and malignant diseases. RESULTS: Postulating a specificity of 95% versus benign diseases of the lung, the diagnostic sensitivity of CYFRA 21-1 in lung cancer (independent of histologic type) at primary diagnosis was superior (47%) to CEA (27%), SCC (15%), and NSE (16%). Especially in squamous cell carcinomas of the lung, the true-positive test results were much higher for CYFRA 21-1 (60%) than for CEA (18%) or SCC (31%). CONCLUSIONS: In small cell lung carcinomas, NSE was confirmed as the marker of first choice. For all of the other solid tumors investigated, CYFRA 21-1 showed no better profile of specificity and sensitivity than the established markers.

Antibodies, Monoclonal↗

Cytokeratin 19 fragments: a new marker for non-small-cell lung cancer.

We developed a new and automated assay for the detection of lung cancer associated cytokeratin 19 fragments in patients' sera/plasma. This new tumour marker assay CYFRA 21-1 was evaluated in technical and clinical studies using the multibatch analysers ES 300 and ES 600 from Boehringer Mannheim GmbH. The analytical performance was shown to be excellent. The clinical data from 2,037 patients demonstrate that for non-small-cell lung carcinoma CYFRA 21-1 has a higher diagnostic sensitivity compared to the established markers. Mainly for squamous cell carcinoma CYFRA 21-1 was superior (60%) to CEA (18%) or SCC (31%).

Biomarkers, Tumor↗

Comparison of cytokeratin fragment 19 (CYFRA 21-1), tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS) as tumour markers in lung cancer.

Recently CYFRA 21-1, a new tumour marker measuring a fragment of cytokeratin 19, was introduced and proved to be suitable for the follow-up care and monitoring of the therapy of non-small cell lung carcinomas, especially squamous cell carcinomas of the lung. Besides CYFRA 21-1, there are two other tumour markers available, called tissue polypeptide antigen (TPA) and tissue polypeptide specific antigen (TPS), which also measure different cytokeratins in serum. In a retrospective study we investigated the clinical significance of these 3 cytokeratin markers in lung cancer compared with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC) and neuron-specific enolase (NSE). We investigated the sera of 50 healthy persons, 273 patients with various benign diseases and 218 patients with histologically proven lung cancer. In a first step the specificity versus benign diseases of the lung was established for all the markers, and was fixed at 95%. Then the single and combined sensitivities were calculated. CYFRA 21-1 proved to possess the highest sensitivity in lung cancer in general (61%), in non-small cell lung carcinomas (64%), in squamous cell carcinomas (79%), in adenocarcinomas (54%) and in large cell carcinomas (65%). In small cell lung carcinomas, neuron-specific enolase proved again to be the marker of first choice (55%). Combined determinations proved clearly increased sensitivity only for large cell carcinomas (CYFRA 21-1 + TPA: 77%) and for small cell lung carcinomas (CYFRA 21-1 + NSE: 62%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Neoplasm↗

Multicenter evaluation of Iso-ALP test kit for measurement of bone alkaline phosphatase activity in serum and plasma.

A test kit (Iso-ALP, Boehringer Mannheim) for measuring human bone alkaline phosphatase activity in serum or plasma was evaluated in five laboratories in three countries. The assay is based on the principle described by Rosalki and Foo (Clin Chem 1984;30:1182-6) and uses wheat germ lectin to precipitate bone alkaline phosphatase. Residual ALP in the supernate in comparison with total ALP is used to quantify the bone fraction. The imprecision of residual ALP measurement was low (median between-run CV 4.9%) and comparable with that of total ALP. Linearity of precipitation was demonstrable up to a bone ALP activity (diethanolamine buffer 37 degrees C) of 2000 U/L, though a matrix effect was observed for dilutions of high-activity sera in saline or bovine serum albumin. For assaying patients' samples, different batches of lectin demonstrated excellent comparability. Taking electrophoresis as a basis for standardization, we determined that the lectin precipitated approximately 90% of bone ALP, but < 5% of nonbone ALP. From this we derived serum/plasma upper reference limits for bone ALP activity in adults and children.

Adult↗

[Prognostic significance of the CA 125 half-life for the further outcome of ovarian cancer].

Since only approx. 30% of patients with ovarian carcinoma present themselves in the early stages, and as a result of the lack of effective screening methods, primary interest has been applied to the improvement of the treatment quality in the later stages. Improvement of therapeutic strategies implies an adaptation of specific characteristics of the patient and the tumour. For instance, in cases of primary progression during chemotherapy, it is not justified to continue an aggressive treatment, which causes additional serious side effects. Surprisingly, it has not been possible, to utilize established or suspected prognostic factors for treatment strategies in ovarian cancer. This might result, in part, from the uncertainty of criteria such as stage of disease, residual tumour and histological grading. The single most relevant prognostic factor today is the residual tumour mass. In 1988 van der Burg suggested for the first time a potential prognostic relevance of the CA 125 half-life. This study was designed, to investigate the use of CA 125 half-life in therapeutic strategies. From January 1984 to June 1990, 346 patients with primary ovarian cancer were treated at our institution. Preoperative CA 125 levels were determined in 292 patients; in 220 patients the levels were complete for a period of more than 6 months so that the CA 125 half-life could be calculated. Survival times of patients with a half-life of less than 20 days were significantly (p less than 0.0001) different from patients with a half-life of more than 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗

Significance of bone alkaline phosphatase, CA 15-3 and CEA in the detection of bone metastases during the follow-up of patients suffering from breast carcinoma.

After the introduction (1, 2) and methodical evaluation (3, 4) of a new method for the quantitative measurement of the bone isoenzyme of alkaline phosphatase (test-combination bone alkaline phosphatase, Boehringer Mannheim), we started a retrospective clinical study for the follow-up investigations of breast cancer patients. Our aim was to establish the significance of the routinely used tumour markers, CEA and CA 15-3, in combination with bone alkaline phosphatase for the early detection of metastatic spread to the bone. We investigated 492 sera from 92 patients suffering from breast carcinoma, and we compared each date of investigation with the results of the clinical examination and with the results of medical imaging, if that had been performed. From a previous study involving skeleton scintigraphy (5) we knew that single examinations do not allow a differential diagnosis between benign and malignant disorders of the bone, so we based our calculations on differences between sequential investigations. We found that in follow-up investigations of patients with breast carcinoma the combined determination of CEA, CA 15-3 and bone alkaline phosphatase may be indicative for the localisation of metastatic disease. The determination of the bone alkaline phosphatase is easy to handle with a short assay time and good reproducibility; it can therefore be recommended.

Alkaline Phosphatase↗