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Biomedical subjects

E Paus

Publications and source records attributed to E Paus.

At least 19 recordsLinked to original sources

Increased serum creatine kinase BB and neuron specific enolase following head injury indicates brain damage.

The aim of this study was to examine whether an increase in the serum concentrations of the two brain enzymes creatine kinase BB (CK-BB) and neuron specific enolase (NSE) can be demonstrated in patients with acute head injury and whether such an increase reflects release from damaged brain tissue. In 60 patients who had suffered minor to severe head injury, serial blood samples were drawn during the first hours after impact, and CK-BB and NSE were measured by radioimmunoassay. Computed tomography (CT) was also performed shortly after admission to hospital, and was repeated 1-3 days later in selected patients. Increased serum concentrations of both CK-BB and NSE were found in 88% of the patients with moderate to severe head injury (group 1, n = 18) and in 23% of the patients with minor head injury (group 2, n = 42), whereas CT showed contusion in only 41% and 2% of the group 1 and 2 patients, respectively. The following findings suggest that the enzymes had been released from brain tissue: 1) The maximum concentrations of CK-BB and NSE correlated with the severity of injury as assessed clinically and with the volume of contusion as estimated from CT (r = 0.79 with CK-BB, r = 0.72 with NSE). 2) The maximum concentrations of CK-BB and NSE were closely correlated (r = 0.87).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Neuron-specific enolase as a prognostic factor in metastatic malignant melanoma.

Serum neuron-specific enolase (NSE) was measured in 63 patients with metastatic malignant melanoma. 20 patients (32%) had elevated serum NSE (> 10 micrograms/l) before the start of treatment. Another 13 patients (21%) developed pathological NSE values during the course of the disease. In many patients, elevated NSE was related to a large tumour burden, and a gradual rise in serum NSE indicated disease progression. Patients with elevated pretreatment NSE had a median survival time of 3 months compared with 12 months for those with normal pretreatment NSE values. NSE thus proved to be a useful prognostic factor in metastatic malignant melanoma.

Biomarkers, Tumor

89Strontium in bone metastases from hormone resistant prostate cancer: palliation effect and biochemical changes.

Hematological and biochemical parameters were evaluated in 31 patients receiving 150 MBq 89Strontium (89Sr) intravenously due to painful skeletal metastases from hormone resistant prostate cancer. Two and 3 months after the injection prostate specific antigen (PSA) had increased by a median of 36% and 100%, respectively, as compared to the pretreatment value whereas alkaline phosphatase (APHOS) had decreased by about 20% (median). The leucocyte and platelet counts were reduced by about 20-35%, without reaching grade greater than or equal to 2 toxicity. Pain relief was reported in 14 of 29 evaluable patients at 2 months and in 11 of 23 patients at 3 months. It is concluded that 89Sr represents a worthwhile therapeutic modality in the palliation treatment of patients with hormone resistant prostate cancer, though the biological significance of frequently increasing PSA and decreasing APHOS is not yet completely understood.

Aged

The prognostic significance of prostate specific antigen in metastatic hormone-resistant prostate cancer.

Twenty-seven of 152 patients (18%) with progressing hormone resistant prostate cancer had normal serum levels of prostate specific antigen (PSA less than or equal to 10 micrograms l-1), when referred for secondary treatment. PSA was significantly correlated with the extent of skeletal metastases (R: 0.35) and the levels of hemoglobin (R: -0.19) and serum alkaline phosphatase (R: 0.30). In a multivariate Cox regression analysis the survival of the 152 patients was not correlated with the PSA level but with the patients performance status, the level of hemoglobin, and the time between primary hormone treatment and relapse. The lack of serum PSA to predict survival may be explained by a heterogenous composition of hormone resistant prostate cancer as regards differentiated and/or PSA producing vs undifferentiated and/or PSA non-producing cells.

Aged

Neuron-specific enolase--a serum tumour marker in seminoma?

The clinical significance of neuron-specific enolase (NSE) as a tumour marker was evaluated in 54 patients with seminoma. Before orchiectomy NSE was elevated in six out of 21 patients with stage I seminoma and 11 out of 16 patients with metastases. After orchiectomy NSE normalised in all evaluated stage I cases, but was still elevated in six out of 12 patients with metastatic disease. NSE monitored the effect of cisplatin-based chemotherapy in patients with metastases. In some patients, increased serum NSE was found together with raised levels of human choriogonadotropin (HCG) and lactate dehydrogenase (LDH), while in others only NSE was elevated. No false positive NSE values were observed. NSE seems to be a clinically worthwhile serum tumour marker for monitoring seminoma patients, with a sensitivity and specificity of the same order as HCG.

Biomarkers, Tumor

Prostate-specific antigen and other prognostic factors in patients with hormone-resistant prostatic cancer undergoing experimental treatment.

In 58 patients with progressive hormone-resistant metastatic cancer of the prostate, prostate-specific antigen (PSA) greater than 100 micrograms/l, haemoglobin less than 12.0 g/dl and pronounced fatigue were found to be independent adverse prognostic factors. These risk factors distinguished a subgroup of patients with a median survival of 9 months (none or only 1 risk factor present) from a subgroup with a median survival of 4 months (greater than or equal to 2 risk factors present). The clinician should be reluctant to enter patients from the second group into complicated and resource-demanding clinical studies, particularly if such trials require frequent and inconvenient follow-up examinations.

Aged

Prediction of pelvic lymph node metastases by a prostate-specific antigen and prostatic acid phosphatase in clinical T3/T4M0 prostatic cancer.

Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in the serum of 69 patients with clinical T3/T4M0 prostatic cancer before staging lymphadenectomy. In principle, high-dose radiotherapy was given only to patients of pathological N0 category. Seventeen patients had a prelymphadenectomy PSA level below the normal upper reference limit (10 micrograms/l) and only 3 of them had pelvic lymph node metastases. Fifteen of 52 patients with a preoperative PSA level > or = 10 micrograms/l were of N0 category. Only 8 of the 41 evaluable patients had PAP values above the normal range, and 6 of these 8 patients had pelvic lymph node metastases. Preoperative PSA values, but not preoperative PAP levels, assist the clinician in predicting regional lymph node metastases in patients with clinical T3/T4M0 prostatic cancer. Two-thirds of the patients with T3/T4 tumours and PSA values between 10 and 50 micrograms/l have regional lymph node metastases. About 80% of the patients with PSA levels < 10 micrograms/l belong to the N0 category. About 75% of the patients with PSA > 50 micrograms/l have N+ disease. Taking into account the individual preoperative PSA values, the indication for preradiotherapy staging lymphadenectomy should be balanced between the chance of demonstrating N+ disease, the expected postoperative morbidity and the benefit for the patient found to be of N0 category.

Acid Phosphatase

Thyroglobulin in patients with differentiated thyroid carcinoma.

Thyroglobulin (Tg) is a sensitive marker for detection of metastatic disease in patients who have been operated on for differentiated thyroid carcinoma. A high serum Tg value during thyroxine suppression therapy is indicative of metastatic disease, but the sensitivity is enhanced by the endogenous TSH response occurring when thyroxine medication is withheld. False-negative values before thyroxine withdrawal can be demonstrated in about 20% of the patients in our material. If not all thyroid tissue has been eradicated the interpretation of the serum Tg can be difficult. Tg cannot be used to differentiate benign from malignant disease prior to surgery.

Biomarkers, Tumor

Neuron specific enolase (NSE) in serum of patients with malignant melanoma.

Serial measurements of serum NSE were performed in 63 patients with metastatic melanoma. NSE was measured by a sensitive immunoradiometric assay based upon monoclonal anti-bodies with monodisperse magnetizable particles as the solid phase. Increased NSE values were found in 30 patients (48%) during the course of the disease. In 10 patients serum NSE normalized during systemic therapy. In 11 patients with initial normal serum NSE, the marker values became elevated as the tumor progressed.

Biomarkers, Tumor

Prognosis in patients with metastatic non-seminomatous testicular cancer.

155 patients with metastatic non-seminomatous testicular cancer were treated with cisplatin-based chemotherapy which in most cases was combined with surgery. The 5 year crude survival was 90% for all patients (98 patients with small volume disease: 97%; 32 patients with large volume disease: 91%; 25 patients with very large volume disease: 64%). High pre-chemotherapy serum tumour marker levels (AFP greater than 500 micrograms/l; and/or HCG greater than 1000 U/l) decreased the survival rates in all groups. Only 4 of 17 relapsing patients were rendered tumour-free by salvage chemotherapy. In a multivariate analysis, a pre-chemotherapy alpha-foetoprotein (AFP) level greater than 500 micrograms/l was associated with poor survival as was the presence of a retroperitoneal tumour greater than 10 cm, lung metastases greater than 3 cm and/or extrapulmonary hematogenous metastases. It is concluded that easily assessable clinical pre-treatment variables can be used to define high risk or low risk patients with metastatic testicular cancer. Treatment intensity should be adjusted in accordance to such prognostic factors.

Adolescent

Flutamide in hormone-resistant prostatic cancer.

Flutamide (250 mg. orally 3 times daily) yielded a subjective response in 5 of 25 fully evaluable patients with hormone-resistant prostatic cancer. Four additional patients had early progression. A 40% or greater decrease in the pre-treatment prostate specific antigen level was observed in 7 of 24 patients and this finding was correlated with improved survival. Toxicity was mainly gastrointestinal and resulted in permanent discontinuation of flutamide in 5 patients. Flutamide or similar antiandrogens may have a role in the management of hormone-resistant prostatic cancer when relief of subjective symptoms should be an important treatment goal together with improvement of survival. However, before the drug should be used routinely in the management of hormone-resistant prostatic cancer phase 3 studies must confirm its effectiveness, especially in comparison to less expensive drugs.

Acid Phosphatase

Early clinical stages (CS1, CS1Mk+ and CS2A) of non-seminomatous testis cancer. Value of pre- and post-orchiectomy serum tumor marker information in prediction of retroperitoneal lymph node metastases. Swedish-Norwegian Testicular Cancer Project (SWENOTECA).

During a 5-year period (1981-86) 588 consecutive patients with nonseminatous germ cell tumors of the testis were included into a prospective Swedish-Norwegian multicenter study (SWENOTECA) and clinically staged according to the Royal Marsden system. A total of 370 patients (63%) had early clinical stages (CS) of disease; 295 (50%) had CS1, 32 (5%) had CS1Mk+ (CS1 with pathological serum tumor marker patterns after orchiectomy) and 43 (7%) had CS2A disease. Pathological staging with retroperitoneal lymph node dissection (RPLND) of the retroperitoneum was performed in 345 (93%) of the early CS patients and 128 (37%) had pathological stage 2 (PS2) disease; 27% of the CS1, 100% of the CS1Mk+ and 66% of the CS2A patients. The overall clinical staging accuracy was 75%. All the 40 patients with pathological serum AFP and/or HCG patterns before RPLND had PS2 disease, compared to 81/282 (29%) of patients with normal marker patterns. The PS2 patients with pathological marker patterns had significantly more and larger retroperitoneal metastases than those with normal AFP and HCG values. Elevated pre-orchiectomy AFP level indicated significantly reduced risk of PS2 disease in CS1 patients, but this effect became non-significant if the CS1Mk+ and CS2A cases were included into univariate or multivariate analyses. We suggest that the 'good risk' effect of pre-orchiectomy AFP elevation for CS1 cases may be caused by a selection mechanism during the clinical staging process.

Biomarkers, Tumor

Is routine primary retroperitoneal lymph node dissection still justified in patients with low stage non-seminomatous testicular cancer?

We present 8 years' experience of primary retroperitoneal lymph node dissection (RLND) in 190 patients with low stage non-seminoma; 154 patients had clinical stage I (CSI) and 36 had clinical stage IIa (CSIIa) disease. Of the 154 patients with CSI tumours, 33 had increased serum AFP and/or HCG before RLND (CSIM+) and 121 had normal tumour markers (CSIM-). Retroperitoneal lymph node metastases (pathological stage II) (PSII) were found in 38 of 121 patients with CSIM-, in 19 of 33 patients with CSIIM+ and in 26 of 36 patients with CSIIa. In a multivariate analysis, the presence of small vessel infiltration (demonstrated in histological sections of the primary tumour) and a prolonged tumour marker half-life were predictive factors for PSII. These 2 factors enabled a group of non-seminoma patients with CSI disease to be identified who had a 15% risk of retroperitoneal tumour growth (low risk group) as compared with a high risk group where 60 to 70% of patients had retroperitoneal lymph node metastases. Relapses occurred in 7 of 107 patients with PSI and in 6 of 83 patients with PSII disease; in the latter group, 5 relapses developed before the start of routine adjuvant chemotherapy; 6% of patients developed major post-operative complications. In addition, "dry ejaculation" was the principal side effect following RLND (unilateral RLND: 20/132 patients; bilateral RLND: 50/54 patients). The comparative cost to the health service during the first year of follow-up was estimated for low risk non-seminoma patients with CSI subjected to RLND and for those in whom a surveillance policy was adopted. The latter approach was preferable. It was concluded that a surveillance policy should be followed in low risk non-seminoma CSI patients provided that frequent follow-up is possible. A more active policy is recommended in high risk patients (e.g. adjuvant chemotherapy without RLND). Nerve-sparing RLND may be considered in patients with CSIIa disease and negative tumour markers.

Adolescent

Histology of tumor residuals following chemotherapy in patients with advanced nonseminomatous testicular cancer.

A total of 111 patients with advanced nonseminomatous testicular cancer underwent cisplatin-based combination chemotherapy, followed by surgical removal of residual masses in 101. Surgery included retroperitoneal lymph node dissection in 92 patients, thoracotomy in 19 and hepatic resection in 1 (11 patients underwent 2 operations). Complete necrosis and/or fibrosis was found in 52 operative specimens, mature teratoma in 37 and vital malignant tumor in 12. Of the 11 patients who underwent 2 operations 4 had complete necrosis and/or fibrosis in both histological specimens. After a median observation of 55 months 83 of 89 patients with complete necrosis and/or fibrosis or mature teratoma were without evidence of disease. Only 7 of 12 patients with vital malignant tumor in the operative specimen survived without evidence of disease. Relapses were observed in 16 patients, 4 of them in the retroperitoneal space. Of the 16 relapses 5 were in 12 patients with residual vital malignant tumor, 5 in 37 patients with post-chemotherapy mature teratoma and 4 in 52 patients with complete necrosis and/or fibrosis after chemotherapy. Two patients with recurrence did not undergo an operation. In patients in whom post-chemotherapy retroperitoneal lymph node dissection is considered complete necrosis and/or fibrosis can be predicted by the combination of several factors, including absence of teratomatous elements in the testicular tumor, complete response on post-chemotherapy computerized tomography, and normal alpha-fetoprotein and human chorionic gonadotropin levels after chemotherapy (sensitivity 83%, specificity 76% and correctly predicted 79%). With the knowledge of these factors it seems possible to omit post-chemotherapy retroperitoneal lymph node dissection in approximately 20% of the patients with advanced metastatic nonseminomatous testicular cancer with initial retroperitoneal tumors.

Adolescent

Establishment and evaluation of a radioimmunoassay for neuron-specific enolase. A marker for small cell lung cancer.

Neuron-specific enolase (NSE) was purified from human brain to a specific activity of 91 U/mg with no demonstrable impurities. The enzyme has a molecular weight of 96,000, consists of two subunits of 47,000, and has an isoelectric point at pH 4.5. A radioimmunoassay based on antibody raised in sheep was established. The assay has a sensitivity of 2 micrograms/l, and an interassay coefficient of variation of 6.4% at 10 micrograms/l. The reference limit was defined as 10 micrograms/l, as found in sera from a population of 389 persons. Of 50 untreated patients with small cell lung cancer (SCLC), 70% had NSE levels above 10 micrograms/l. None of 170 patients with non-SCLC neoplasms had elevated enzyme levels.

Adult

Immunoradiometric assay for alpha gamma- and gamma gamma-enolase (neuron-specific enolase), with use of monoclonal antibodies and magnetizable polymer particles.

Monoclonal antibodies were raised against neuron-specific enolase, gamma gamma-enolase, and used in an immunoradiometric assay (IRMA), with mono-disperse magnetizable particles as the solid phase. The assay's sensitivity was 0.4 microgram/L and the interassay coefficient of variation was less than 5% in the working range from 0.4 to 170 micrograms/L. Compared with our radioimmunoassay based on polyclonal antibodies, the incubation time is shorter, and precision and sensitivity are improved. The IRMA also improved detection of neuron-specific enolase in sera from patients with lung cancer without a concomitant change in measured enolase in the reference population. The better sensitivity of the IRMA results from its ability to measure alpha gamma- and gamma gamma-enolase with equal response. Ninety percent of the small-cell lung carcinoma patients (36 of 40) had increased values before treatment, compared with 7% of non-small-cell lung carcinoma patients (8 of 114).

Animals