Microinvasive germ cell tumour (MGCT) adjacent to testicular germ cell tumours.

AIMS: To examine the occurrence and prognostic significance of intratubular germ cell neoplasia (IGCN) and microinvasive germ cell tumour (MGCT) in tissue adjacent to testicular germ cell tumours (TGCT) in adults. METHODS AND RESULTS: The study was based on two Danish studies of adult patients with stage I TGCT and included 255 patients. Of 106 patients with seminoma, 75 [71%, 95% confidence interval (CI) 61, 79] had IGCN without MGCT and nine (8%, CI 4, 15) had both IGCN and MGCT. Of 149 patients with non-seminoma, 62 (42%, CI 34, 50) had IGCN without MGCT, and 32 (22%, CI 15, 29) had both IGCN and MGCT. Non-seminomas with a seminoma component were more often associated with MGCT (23 of 54 testes, 43%, CI 29, 57) than were non-seminomas without this component (nine of 95 testes, 10%, CI 4, 17) (P < 0.000 05, Fisher's exact test). Relapse-free survival was not influenced by the concomitant presence of the two precursor stages in the testes (P = 0.36, and P = 0.19, log rank test, respectively). CONCLUSIONS: MGCT was a relatively frequent finding in testes adjacent to a macroscopic TGCT. However, neither IGCN nor MGCT predicted relapse for patients with stage I TGCT.

Intra-abdominal obesity and metabolic risk factors: a study of young adults.

OBJECTIVE: To assess the relative importance of the extent and regional distribution of fat for metabolic risk factors in young adults. DESIGN: Cross-sectional study of findings from a hospital-based case-control study. SUBJECTS: A total of 46 adult Danish Caucasian patients (40 men and six women, aged 34-54 y). Of these, 22 had had non fatal acute myocardial infarction before 41 y of age and 24 were age- and gender-matched controls without coronary heart disease. MEASUREMENTS: Four measurements of fat: body mass index (BMI, kg/m(2)), body fat percentage measured using a dual energy X-ray absorptiometry (DEXA) scanner, waist/hip circumference ratio (WHR), and intra-abdominal adipose tissue area measured using computed tomography (CT) scanning, and eight metabolic risk factors: systolic and diastolic blood pressure, HbA(1c) percentage, fasting concentrations of capillary whole blood glucose, high-density lipoprotein (HDL) cholesterol, serum triglyceride, plasma plasminogen activator inhibitor 1 (PAI-1), and urinary albumin:creatinine excretion ratio. RESULTS: Of 46 participants, 10 were obese (BMI >30 kg/m(2)), 12 were abdominally obese (WHR >0.90 for men and >0.85 for women), and 20 were intra-abdominally obese (intra-abdominal adipose tissue area >135 cm(2)). Men had a higher intra-abdominal adipose tissue area than women (P=0.0053, Mann-Whitney U-test). In multiple regression analyses of the four fat variables, only intra-abdominal adipose tissue area significantly predicted the levels of six metabolic risk factors: systolic blood pressure, diastolic blood pressure, fasting concentrations of capillary whole blood glucose, serum HDL cholesterol, serum triglyceride, and PAI-1. The intra-abdominal adipose tissue area had a linear relation with the six metabolic risk factors. CONCLUSIONS: For young individuals, intra-abdominal fat is the important component of the body fat for six of the eight metabolic risk factors. Intra-abdominal fat might contribute to that most patients with acute myocardial infarction at a young age are men.

A systematic review of lactate dehydrogenase isoenzyme 1 and germ cell tumors.

OBJECTIVES: To evaluate lactate dehydrogenase isoenzyme 1 (LD-1) as a tumor marker of germ cell tumors. METHODS: A literature search included a CancerLit and Medline computer search of articles regarding germ cell tumors and LD-1 published between 1963 to 99 and a manual search of reference lists, theses, and textbooks. Forty articles, letters to the editor, and abstracts on testicular germ cell tumors and 10 articles on ovarian germ cell tumors fulfilled inclusion criteria. RESULTS: Of 696 patients with testicular germ cell tumors, 423 (61%) had a raised serum LD-1 catalytic concentration (S-LD-1). Patients with seminoma have a raised S-LD-1 more often (63%) than those with nonseminoma (60%). S-LD-1 was raised less often in patients with stage I (48%) than in those with stage II (50%) and stage III (67%). S-LD-1, serum alpha fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) were discordant. S-LD-1 predicted outcome in four studies: one study regarding relapse in patients with nonseminomatous testicular germ cell tumors stage I, and three studies regarding survival of patients with metastatic testicular germ cell tumors. In two of three studies, S-LD-1 was a better prognostic predictor for patients with metastatic testicular germ cell tumors than S-LD. Of 40 patients with ovarian germ cell tumors, thirty-five (88%) had a raised S-LD-1. CONCLUSIONS: S-LD-1 is a useful serum tumor marker of testicular germ cell tumors. For patients with ovarian germ cell tumors, S-LD-1 was raised more often than for patients with testicular germ cell tumors. Further studies are required for a general recommendation regarding the use of S-LD-1 for germ cell tumors.

Serum lactate dehydrogenase isoenzyme 1 and relapse in patients with nonseminomatous testicular germ cell tumors clinical stage I.

Serum lactate dehydrogenase isoenzyme 1 catalytic concentration (S-LD-1) was measured at the time of orchiectomy in 104 patients with nonseminomatous testicular germ cell tumors (NSTGCT) clinical stage I who participated in a randomized study comparing surveillance after orchiectomy (group I) and radiotherapy (group II). For 68 patients, S-LD-1 was measured in a serum sample before or on the day of the orchiectomy. Twenty-seven patients (40%) had elevated S-LD-1; median 102 U/L (range 41-335). For the remaining 36 patients. S-LD-1 was measured in a serum sample after orchiectomy: 8 of these patients (22%) had elevated S-LD-1. S-LD-1 was normalized shortly after surgery in most patients with a preorchiectomy elevated S-LD-1. Fifteen of the 68 patients relapsed: 9 out of 27 with an elevated S-LD-1 and 6 out of 41 patients with normal S-LD-1 (p = 0.13, Fisher's exact test). In group 1, those with a preoperatively elevated S-LD-1 had a lower 8-years' relapse-free survival than those with a normal S-LD-1 (40% vs. 80%, p = 0.003, log-rank test). The role of S-LD-1 in the staging, prognostication and monitoring of patients with NSGCT clinical stage I should be further explored in a large, prospective study.

Smoking and other major coronary risk factors and acute myocardial infarction before 41 years of age: two Danish case-control studies.

OBJECTIVE: The aim of two case-control studies of adults younger than 41 years of age was to assess how the major coronary risk factors, family history of acute myocardial infarction (AMI), obesity, hypertension and hypercholesterolemia add to the risk of AMI from self-reported current smoking (smoking). DESIGN: An evaluation study included 35 patients and 70 individually matched controls. RESULTS: The risk from smoking increased less than linearly and the risk from serum cholesterol concentration (cholesterol) increased linearly. In multiple conditional logistic regression analyses, smoking as a discrete variable and cholesterol as a continuous variable were significant coronary risk factors. In a final logistic regression model, the odds ratio was 6.4 (95% confidence interval (CI) 1.7-24.1) for smoking and 1.6 (CI 1.1-2.3) for each mmol/L cholesterol. A risk score summarizing the combined risk of the major coronary risk factors did not add to the final logistic regression model (p = 0.56). A validation study included 79 patients and 64 matching control patients. CONCLUSION: The major coronary risk factors were similar for the cases/patients and the two control groups in the two studies. Therefore, the final logistic regression model may reflect a general pattern in Denmark. Primary prevention in individuals less than 41 years of age should focus on smoking and cholesterol instead of the summarizing risk score.

Serum lactate dehydrogenase isoenzyme 1 and prediction of death in patients with metastatic testicular germ cell tumors.

The International Germ Cell Cancer Collaborative Group study of patients with metastatic testicular germ cell tumors showed that catalytic concentration of serum lactate dehydrogenase (S-LD), serum alpha-fetoprotein concentration (S-AFP), and serum human chorionic gonadotropin concentration (S-hCG) predicted death from tumor. The recent international TNM classification (T primary tumor, N lymph node metastasis, M distant metastasis) is based on these results. The aim of our study was to evaluate whether catalytic concentration of S-LD isoenzyme 1 (S-LD-1) was a better predictor than the criteria used for the international classification. In an evaluation series of 44 patients from Odense University Hospital, Denmark, a raised S-LD-1 (>1.0 x upper limit of reference values) had a predictive value for death from tumor in 5-years observation of 46%. The predictive value was 46% for S-LD, 25% for S-AFP, and 40% for S-hCG. A normal SLD-1 had a predictive value for survival over 5-years observation of 100%. It was 81% for S-LD, 75% for SAFP, and 77% for S-hCG. The fraction of the patients who died of tumor and had a raised tumor marker value was 100% for S-LD-1, 46% for S-LD, 9% for S-AFP, and 18% for S-hCG. The fraction of patients with a normal serum tumor marker value among those who survived was 61% for S-LD-1, 81% for S-LD, 94% for SAFP, and 94% for S-hCG. A validation series of 37 patients treated at the University of Texas MD Anderson Cancer Center showed similar findings. Combining the patients in the two series, a raised value of SLD-1 classified more patients into a subgroup with an impaired survival (53%) than S-LD (35%), S-AFP (6%), or S-hCG (11%), and the high risk subgroups based on the international classification (40%). The findings have implications for the staging and treatment of patients with metastatic testicular germ cell tumors.

Lactate dehydrogenase isoenzyme 1 is the most important LD isoenzyme in patients with testicular germ cell tumor.

We examined the clinical utility of serum lactate dehydrogenase (LD) isoenzyme catalytic concentrations in 58 patients with testicular germ cell tumors (TGCT) (13 with seminoma and 45 with non-seminomatous tumors). Twenty-one patients with no evidence of disease (NED) all had serum LD isoenzyme 1 catalytic concentrations (LD-1) and LD-1/LD fractions below the upper limit of the reference values (ULR). LD-1 and the LD-1/LD fraction discriminated significantly between evidence of disease (ED) and NED (p = 0.00009 and p = 0.028, respectively, Mann Whitney U-test). Twenty of the 37 patients with ED had raised values of LD-1. The 17 patients with an LD-1 < 1.0 x ULR had a better survival than the 10 patients with LD-1 between 1.0 and 2.9 x ULR, the 7 with LD-1 between 3.0 and 5.9 x ULR, and the 3 patients with LD-1 > 6.0 x ULR (p = 0.006, log-rank test, chi2 test for trend)). Twenty-three patients with an LD-1/LD fraction < or = 0.25 had a better survival than the 14 with an LD-1/LD fraction > 0.25 (p = 0.013). Nineteen patients with LD-5 < 105 U/L and the 15 with LD-5 > 105 U/L had a similar rate of survival (p = 0.85). Our findings add to the evidence showing LD-1 in preference to LD as a serum tumor marker of TGCT.

Analytical quality specifications for serum lactate dehydrogenase isoenzyme 1 based on clinical goals.

The aim of the study was to deduce analytical quality specifications for the determination of catalytic concentration of serum lactate dehydrogenase isoenzyme 1 (S-LD-1) according to clinical goals (the clinical utility model). We defined clinical goals for false positive and false negative S-LD-1 measurements in the monitoring of patients with testicular germ cell tumors (TGCT), clinical stage I, on a surveillance only program. The absolute S-LD-1 catalytic concentrations were routinely corrected for contamination from preanalytical hemolysis. A reference group of 37 men had a near In-Gaussian distribution for the absolute S-LD-1 catalytic concentration. The geometric mean was 76 U/l and an S-LD-1 >128 U/l (99.72 percentile, the decision limit) indicated a high risk of a relapse of TGCT. We have previously shown that an S-LD-1 >160 U/l (treatment limit) was associated with a suboptimal outcome from the treatment of metastatic TGCT. The maximum allowable analytical positive bias was 5 U/l, and the maximum allowable analytical negative bias was -32 U/l. The maximum allowable analytical coefficient of variation, CV(A), was 11% (approximately 14 U/l) at a bias = -5 U/l. For S-LD-1 measurements not corrected for hemolysis, the decision limit was 145 U/l, the maximum allowable negative bias -19 U/l, and CV(A) 8%(approximately 12 U/l). A routine correction for hemolysis had a large impact on the analytical quality specifications.

Serum lactate dehydrogenase isoenzyme 1 as predictor of tumor-associated death in patients with testicular germ cell tumours.

Serum lactate dehydrogenase iso-enzyme 1 (S-LD-1) was determined in 24 patients with testicular germ cell tumours who died during follow-up. Serum samples were obtained at the start of chemotherapy or late into the clinical course for those without evidence of a tumour. Seven of the eight patients with tumour-associated death had S-LD-1 > 150 U l-1 (median 260 U l-1 range 90-905 U l-1, as did two of the six who died without evidence of a tumour (median 134 U l-1 range 89-128 U l-1) (P = 0.03, Mann-Whitney U-test, two-tailed). The remaining 10 patients had previously been reported as to prediction of S-LD-1 for the prognosis, and were evaluated only as to the reproducibility of the S-LD-1 determination. S-LD-1 was determined in two serum samples obtained concomitantly from eight of these 10 patients: the difference between the two S-LD-1 determinations was median 6% of the average of the two S-LD-1 determinations (25-75% range 3-17%). Our study showed an unforeseeable high level of imprecision of the assay system. Nevertheless, S-LD-1 determinations in the regular monitoring of patients with testicular germ cell tumours may be useful for predicting tumour-associated deaths.

High prevalence of smoking in young patients with acute myocardial infarction.

Of 35 patients with acute myocardial infarction (AMI) at the age of 40 years or less, 32 (91%) smoked and only three patients were non-smokers. The age at AMI related significantly to the extent of smoking (p < 0.001, Kruskall-Wallis test). Five patients with AMI at the age < 30 years smoked more heavily than the 30 with AMI at the age of 30-40 years (p = 0.04, Mann Whitney U test). Heavy smoking men > 30 years at the AMI had a Q-wave infarction as often (11 of 13 (85%)) as those with multivessel disease or a coronary artery occlusion (8 of 9 (89%) and 14 of 16 (88%) respectively) on coronary arteriography after the infarction. Smoking may be the most important modifiable risk factor in young patients with AMI.

[Computer tomography in Greenland--a basis for establishment of the service]. / Computertomografi i Grønland--basis for hjemtagelse.

The purpose of this study is to evaluate the consequences of referral of patients for medical reasons from Greenland to Denmark for computed tomography (CT) scans. Twenty-eight of 35 evaluable patients could have been treated following the information from the CT scans without the use of the resources of a university hospital (for instance rehabilitation of patients with cerebral infarction). The establishment of a CT scanning service in Greenland may reduce costs without a deterioration in medical care. Accordingly, the alternative seems attractive.