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Objective: The strategies for combining two screening tests for HIV infections in blood or plasma donors are formulated in biometric terms and analyzed with respect to their value, i.e. their validity, cost and effectiveness., Design: Biometrical modeling using assumptions on the validity of the single tests, the conditional correlations between them, as well as on the cost of testing and the consequences of false-negative or false-positive test results., Results: If the test combination is defined as positive whenever at least one of the single tests is positive, then this rule (the 'believe the positive' rule, BTP), due to its lower specificity, has extremely low positive predictive values. In case of high prevalence rates of the infection (e.g. 1:1,000), the BTP rule leads to lower total cost than single testing, unless the latter has very high sensitivity (e.g. 99%). For smaller prevalence rates (< 1:50,000), which are more typical of the selected group of blood or plasma donors, combination testing is of little value because the extra cost of detecting one additional infection (compared with single testing) may reach several 100 million DM., Conclusion: The cost for detecting additional cases of HIV infection by using combination instead of single testing in HIV screening is so high that this decision requires a public consensus.

Numerous trials have shown, that breast cancer have highly variable rates of growth. It is assumed, that the rates (relative growth rates) decelerate with increasing tumour size. The Universities of Heidelberg and Louisville carried out a retrospective statistical analysis of the mammographically measured growth rates of 448 screening patients until breast cancer diagnosis. The analysis did not include fast-growing carcinomas appearing between mammograms for which only one mammogram was available or some cancer, where growth was not detectable by mammography. Generalized logistic curves provided the best fit to the data on the increase in tumour size, as observed in mammograms. Large variations in individual tumour doubling times were found, from extremely fast-growing to extremely slow-growing tumours. The results are relevant for patient prognosis, for the evaluation of therapy, and for screening strategies.

Epidemiologic case-control studies have suggested an inverse relationship between past medical history of frequency of common colds and subsequent cancer risk for various sites. One hypothetical explanation for this finding may be that there are unknown differences in immune responsiveness between patients developing cancer and healthy individuals. The present study examines the relationship between the frequency of common colds and a) plasma levels of sICAM-1/CD54, sLFA-3/CD58 and sIL-2R/CD25 which are believed to modulate activation of immune responses, and b) cell-mediated immunity in vivo as determined by Multitest Mérieux. The investigation was conducted as a correlation study amongst a healthy group of individuals from the general population in Germany. We found a statistically significant inverse relationship between frequency of common colds and levels of sCD58 and, partially, sCD54. No association was found between levels of sCD25 and results of Multitest Mérieux.

The association between the frequency of manifest infectious diseases and cancer risk was investigated in a case-control study at Heidelberg, FRG. A total of 255 cases with carcinomas of the stomach, colon, rectum, breast, and ovary, as well as 255 population controls and 230 hospital controls were interviewed using a standard questionnaire. Controls were matched to the cases for age, sex, and region of residence at the time of the interview. A history of common colds or gastroenteric influenza prior to the interview was found to be associated with a decreased cancer risk. Thus the odds ratios for "three or more common colds per year (on average)" versus "no common cold within the last 5 years prior to the interview" were 0.18 (95% CI = 0.05-0.69) and 0.23 (95% CI = 0.06-0.89) relative to population controls and hospital controls, respectively. There was no apparent relationship between childhood infections or other diseases reported in the earlier history, and cancer risk. While the findings are supported by previous studies and fit well into the results of other fields of cancer research, a conclusive interpretation and biological explanation cannot yet be given.

In Crohn's disease (CD) the intestinal lesion is supposed to be the cause of the observed systemic immunologic changes. Based on this assumption, peripheral blood mononuclear cells (PBMC) are of specific interest as a possible indicator of intestinal activity of the disease. From 151 surgical patients CD3+, CD4+, CD8+, B cells, macrophages, leucocytes and the relative number of lymphocytes were analysed preoperatively and 10 days, 3 and 6 months postoperatively. The cell data were correlated with the main clinical data of disease. There was a highly significant preoperative increase of leucocytes, macrophages, CD8+, and B cells in the CD group, and a marked decrease of CD3+, CD4+ cells, and the relative lymphocyte count in the same group. Six months postoperatively, highly elevated macrophages, and leucocytes, and a depressed number of CD4+ cells were the only changes. The preoperative cell data did not correlate with the duration of illness, CDAI, localisation, and extent of the intestinal lesion nor did they correlate with any modality of preoperative drug treatment. Thus, the determination of PBMC characteristics in CD is only of limited value for routine diagnostic purposes. However, the persistence of some pathological values long after operation might be caused by residual microscopic lesions and thus reflect the intestinal process.

There is no agreement in literature on the biological behavior of psammoma carcinomas of the ovary. The majority of authors consider psammoma bodies to be the result of tumour regression, associating the occurrence of psammoma bodies with longer survival. On the other hand, several studies reveal a poor prognosis for psammoma carcinomas, similar to that of other epithelial malignant tumours. In our study, the psammoma body content in 174 serous carcinomas stage III/IV was morphometrically quantified by image analysis and the results correlated to survival time and progression time. In 20 carcinomas the psammoma body content was extremely high. In such cases, DNA flow cytometry revealed these tumours to be slowly-growing. The DNA index was 1.0 (DNA-diploid) and the number of S phases was low (max. 5.9%). The five year estimate survival was 50%, as opposed to 10% for other tumours. If no methods are available for cell kinetic analysis and for objectification and quantification of psammoma body content in serous carcinomas it is sufficient to make a semiquantitative assessment of the psammoma body content to differentiate tumours with longer survival from carcinomas of poor prognosis.

The purpose of this study was to compare the value of different imaging methods (radiography, computer tomography and scintigraphy) for demonstrating pulmonary fibrosis or radiation pneumonitis. The right lungs of 50 rabbits were irradiated with 3200 to 6200 rd. The lung changes were observed by the above methods over a period of 13 weeks. Histological examination served as the basis for evaluating the imaging methods. The comparison demonstrated the superiority of computer tomography when density measurements were included in the diagnostic criteria. The accuracy was about 95%. Scintigraphy was inferior to computer tomography as a quantitative method, using differences in the counts per unit area. Radiology as a subjective method achieved an accuracy of about 84%, approximately the same as scintigraphy.

The literature data about the distribution of mononuclear cells in Crohn's disease are still contradictory. In 50 surgical C.D. patients, clinically classified corresponding to the Crohn's Disease Activity Index (CDAI), the T-lymphocytes and their subsets helper-T- and suppressor-T-lymphocytes (TH/TS) were therefore determined by use of monoclonal antisera, the B-lymphocytes by F(a b)-anti human Ig and the macrophages by uptake of latex microparticles. 37 C.D. patients underwent diseased bowel removal. Blood was drawn from the Crohn-draining mesenteric vein for analysis. Further investigations were performed at the 10th p. op. day as well as after an average period of 7 months (2-18). In comparison the mononuclear cell distribution was examined in 14 patients suffering from chronic osteitis and in 14 patients without any inflammatory disease as controls. C.D. patients showed preoperatively a significantly decreased TH/TS-ratio as well as a significantly increased proportion of macrophages. There was a lymphocytopenia in the peripheral differential blood count. Whereas the distribution of mononuclear subpopulations in the mesenteric blood was identical to the peripheral blood, significant lymphocytosis in the differential blood count of mesenteric blood was found. On the 10th p. op. day the TH/TS-ratio rose almost up to normal, which continued during the follow-up period. The macrophages remained constantly increased in all stages of investigation although during the follow-up none of the patients had signs of disease recurrence. Osteitis patients showed a similar distribution as C.D. patients, even if the changes compared to controls were not as distinct. The proportion of B-lymphocytes was the same in all groups examined. The individual TH/TS-ratios and proportions of macrophages of C.D. patients did not correlate to their clinical data. The changes within the T-cell-subpopulations seem to reflect less M. Crohn's disease itself than its inflammatory complications. Further studies have to be undertaken concerning the impact of the constant increase in macrophages, even after resection of the Crohn bearing bowel segment.

From January 1978 to December 1980, 222 patients with metastatic breast cancer were included into a prospective multicenter trial. All patients were treated once a month with six cycles of VAC- (vincristine, adriamycin, cyclophosphamide) chemotherapy, followed by FMC (5-fluorouracil, methotrexate, cyclophosphamide) until progression was documented. By random assignment, the patients received immunostimulation with Corynebacterium parvum (CP) by one of four methods: subcutaneous (SC) on either day 1 or day 14, intravenous (IV) on either day 1 or day 14. The 214 evaluable patients were equally distributed to the four arms. The rates of complete or partial response to VAC/FMC plus CP did not differ significantly between the treatment groups. Of our patients, 22-33% were definite treatment failures. The Kaplan-Meier curves of duration of remission (medians 14 vs. 9 vs. 13 vs. 11 months) did not differ significantly. Only small differences in survival were noted among the four study groups (medians 15.4 vs. 17.5 vs. 17.2 vs. 13.0 months). However, complete and partial responders lived significantly longer (Log rank test P = 0.008), when CP was given on day 14 by the SC rather than IV route (29+ vs. 14.3 months). Patients in the four study groups were treated with virtually identical doses of VAC/FMC chemotherapy. Patients receiving CP intravenously on day 14 experienced significantly lower mean leukocyte counts than patients in the other groups. Many patients suffered from high temperature (requiring treatment with antipyretics) and severe gastrointestinal toxicity, particularly when CP was given IV on day 1 together with the chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

In a prospective non-randomised trial 1642 patients were included. After a mean time of 10 years a follow-up analysis was performed. The importance of the radicality of the primary operative therapy of breast cancer should be evaluated. The mean 5 years survival rate was 67.3%, the 10 year survival rate 51.6%. Tumor stage and age had a highly significant influence on the survival rate. Patients with simple mastectomy had a lower survival rate as patients with radical mastectomy. This apparent difference was caused by a different age distribution in the therapy groups. Accordingly the mean life deficiency was the lowest in the simple mastectomy group. In a multiple hazard statistical analysis tumor stage and age showed a highly significant influence on the survival rate. The intraoperative radicality classification showed a significant correlation to the prognoses of the patients. The operative therapy itself had no significant influence on the survival rate of the patients.

115 rabbits were irradiated with our usual fractionation scheme, and the dose effect curves for fast neutrons and photons (60Co) were determined with respect to pneumonitis and pulmonary fibrosis, respectively. On comparison of the radiogenic alterations three months after therapy, the relative biological effectiveness calculated by means of these dose effect curves was 2,9 for the fast neutrons. Furthermore, the authors tested the conformity of some clinical examination methods such as X-ray, scintigraphy and computed tomography with histological findings of pneumonitis and pulmonary fibrosis, respectively. In this regard, computed tomography was superior to the other examination methods.

Tissue samples from 49 women with seven benign and 42 malignant ovarian tumors were examined by means of DNA flow cytometry (FCM). The FCM data (DNA-ploidy and the number of S-phase fractions) were compared with the International Federation of Gynecology and Obstetrics (FIGO) stage, the histologic grade of differentiation and in some cases with the clinical outcome. The benign ovarian tumors were all diploid with a mean of 2.1% (+/- 1.66) S-phase fractions. Adenocarcinomas with the histologic grade 1 were diploid and had a mean of 2.1% (+/- 1.17) S-phase fractions. Grade 2 adenocarcinomas were aneuploid in eight of nine cases and revealed an increased proliferative activity (7.7% +/- 2.67 S-phase fractions). A high number of aneuploid cases (nine of 13) and an increased DNA synthesis were found in grade 3 adenocarcinomas (12.0% +/- 5.72 S-phase fractions). Four of six malignant nonepithelial tumors also had high numbers of S-phase fractions (9.7-14.5%). A significant correlation between the histologic grade and the DNA synthesis, FIGO stage, and DNA-ploidy was found. DNA-FCM may be used as an additional diagnostic tool supplementing routine histopathologic examination of ovarian tumors for better biological characterization, especially for those with uncertain grading, for grade 2 neoplasms, and for malignant nonepithelial tumors.

The prognostic significance of DNA flow cytometric examinations of 247 patients (mean age 57 years; 27-84) with operable breast cancer was analyzed. The findings were compared with biochemically determined steroid-hormone receptors and lymph node status. Forty-two percent of the tumors were diploid and 58% aneuploid; 32% of them had a high S-phase portion (greater than 5%; definition by the crit-level method). S-phase fractions were lower in diploid than in aneuploid tumors (2.5 +/- 2.2% versus 5.5 +/- 3.4%). Both with diploid tumors as well as tumors with a low S-phase fraction (less than 5%), recurrence-free survival was better than with aneuploid tumors (p = 0.02) and tumors with a high S-phase fraction (p = 0.004). A direct proportional relationship was found between the S-phase fraction and the mean recurrence-free interval. As regards overall survival, no significant differences have been detected so far, either for diploid and aneuploid tumors or tumors with low and high S-phase fractions. Using the Cox regression model, the prognostic significance of ploidy status and S-phase, as new factors, independent of age, lymph node and steroid-hormone receptor status, is shown. DNA flow cytometry is suitable for routine clinical use and should be used in particular as an independent prognostic factor for planning and stratification in adjuvant therapeutic studies.

In a phase-III study in non-Hodgkin's lymphoma of low malignancy we compared a combination therapy with vincristine (COP) with a vindesine combination (CEP). Remission rates, duration of remission and survival was favorable for the CEP combination without reaching the level of significance. The peripheral neurotoxicity of grade 2 and 3 according to WHO criteria was observed more frequently with vincristine. The vincristine-induced neurotoxicity in 6 patients was not impaired when a change was made to vindesine treatment.

A total of 156 patients with metastatic breast cancer were entered into a prospective multi-center trial in September 1975. All patients were treated monthly with vincristine, adriamycin and cyclophosphamide (VAC) six times, followed by 5-fluorouracil, methotrexate and cyclophosphamide (FMC) until progression was documented. By random assignment, the patients received 5 mg/m2 Corynebacterium parvum (CP) subcutaneously on day 1, in addition to VAC/FMC. Of the 150 evaluable patients, 33 of 76 (45%) and 36 of 74 (49%) had complete or partial response to VAC/FMC plus CP, respectively. The Kaplan-Maier curves of duration of remission and survival were almost identical (medians 14.5 vs 12.1 months and 22.2 vs 21.1 months, respectively). The hematologic and gastrointestinal toxicity were also similar in the two study groups. However, 19 of 74 (26%) patients developed skin ulcers after repeated injections of CP. These patients showed prolonged survival (P = 0.002, log rank test). These results suggest that adding nonspecific immunostimulation with CP to currently available chemotherapy on day 1 is of no benefit to most patients with metastatic breast cancer, but may select an "immunoreactive subgroup with increased local toxicity and survival.

Fast neutrons are only superior to photons if their relative biologic effectiveness (RBE) is higher within the tumor than in sound organs. It was therefore the object of this study to test the effects and side effects of rapid neutrons in an especially appropriate tumor model. The bronchial carcinoma was chosen because, according to radiobiologic experiences, the relative biologic effectiveness of neutrons is significantly higher in the Lewis bronchial carcinoma than in the normal lung. These experiences showed furthermore that, compared to other organs, the lung is relatively unsensitive to neutrons, so that the conditions for a treatment with this new type of radiation are favorable. Despite these favorable conditions, no local superiority of neutrons with respect to photons could be established by a clinical study including 115 cases. It shall be examined in a further study if a therapeutic advantage can be realized by a combination of neutrons and photons.

80 patients with inoperable non-small cell bronchial carcinoma were treated, at an interval of 4 weeks between them, with ifosfamide (2 g/m2 on days 1-5) and cisplatin (75 mg/m2, day 1). All diagnoses had been confirmed histologically. The course of 72 patients (36 with squamous carcinoma, 25 with adenocarcinoma, two with alveolar-cell carcinoma and nine with large-cell carcinoma) could be evaluated. There were four complete and 21 partial remissions (response rate 35%). In a further 14 patients temporary arrest of tumor growth was registered. Median survival time of all patients was 8.3 months, for those with complete and partial remission 11.5 months. Patients in whom the tumor progressed lived on average 3.9 months. Age and general state of the patients, as well as histological tumor type, had no influence on the results of treatment. Patients in stage IV lived, at seven months, significantly less long than those with only loco-regional spread (11 months). Main side-effects were vomiting, bone-marrow depression and neuropathy. Urotoxicity was not significant, as a result of treatment with mesna. Remission rate and survival time of these patients corresponded with the results obtained with other cisplatin combinations.

A total of 233 primary carcinomas of the breast (n = 68 nodal negative and n = 165 nodal positive) of 77 woman patients of less than 50 years of age and pf 156 women patients of 50 years of age or older were examined for the prognostic significance of a proliferation index (in vitro chemoresistance assay). The prognostic significance of the proliferation index (high vs low proliferation) is compared with other prognostic factors that have already been in clinical use (age, axillary lymph node status, oestrogen and progesterone receptor status). The total median observation period was 4.8 years (3-9.1 years). Determination of the proliferation index proved to be the most important prognostic factor both for premenopausal and postmenopausal, nodal negative and nodal positive primary tumours when assessing the total survival time and the time that remains free from recurrences. A simultaneous assessment of low proliferation index and positive hormone receptor as a so-called low-risk situation shows in comparison to a high-risk situation (high proliferation index, negative receptor status) the most pronounced differences. For premenopausal women (younger than 50 years of age) the hormone receptor status has no prognostic significance as far as our group of patients is concerned, whereas for women of 50 years of age or older the receptor status is of great prognostic relevance. Besides the lymph node status, the proliferation index shows in a Cox regression model the greatest prognostic importance for the further course of a primary carcinoma of the breast.(ABSTRACT TRUNCATED AT 250 WORDS)

In 120 patients suffering from carcinoma of the endometrium of a wide variety of histological types, conventional clinical and morphological criteria of prognosis were compared with the DNA index (DI) and the S-phase fraction. The cellular kinetics parameters were obtained via flow cytophotometry. Adenocarcinomas (n = 101) were more frequently DNA diploid and had a lower S-phase share (less than 5%) than adenoacanthomas, clear-cell carcinomas and malignant Müller's mixed tumors. There are close correlations between the conventional prognostic factors such as FIGO stage, relative tumor invasion depth, grading and oestrogen or progesteron receptor content and the DNA content or S-phase fraction. Carcinomas with a DI less than or equal to 1.1 (n = 83) and the S-phase fraction less than 5% (n = 77), have a significantly longer survival time and recurrence-free interval than DNA-aneuploid tumors with a high S-phase fraction. The studies underline the need to use flow cytophotometry in the prognostic assessment of the carcinoma of the endometrium. The method is superior to histological grading, since the results obtained can be objectively assessed.

In all, 171 patients with histologically verified non-small cell lung carcinoma were treated with ifosfamide 2.0 g/m2 on days 1-5 in combination with (91 patients) etoposide 120 mg/m2 on day 1. Therapeutic regimens were repeated after 4 weeks. Supportive treatment with mesna (20% of the ifosfamide doses at 0, 4, and 8 h) was performed. Cisplatin treatment was supported by mannitol-induced diuretic hydration. The overall response rate of ifosfamide/etoposide was calculated to be 27%, with 1 complete and 24 partial remissions. The median survival time for all patients was 8.5 months, for responders 14 months (P less than 0.05), for patients with no change 9.5 months, and for patients with tumor progression 4 months. With ifosfamide/cisplatin, there were 4 complete and 21 partial remissions (response rate 35%). The median survival time for all patients was 8.3 months, for responders 11.5 months, and for patients with tumor progression 4 months. Age, sex, and histological tumor type had no significant effect on survival. Patients with better performance stage and limited disease lived significantly longer. The main side-effects of the cisplatin combination were vomiting, bone marrow depression, and neuropathy. The etoposide combination was tolerated better. Urotoxicity was not significant, as a consequence of treatment with mesna. The results show that the combination ifosfamide/etoposide or ifosfamide/cisplatin are effective in the treatment of non-small cell lung cancer, being comparable to other combinations of etoposide/cisplatin and vindesine/cisplatin. Because of the better tolerability, the combination ifosfamide/etoposide is superior to cisplatin combinations.

Parenchyma-preserving resection techniques are grouped into two categories: (1) Broncho- and angioplastic resections that help avoid pneumonectomy and (2) Wedge or segment resections that help avoid lobectomy. The indications are: (a) Elderly patients (70 years); (b) Impaired respiratory reserve; (c) Palliative surgery; (d) Limited tumour growth. The analysis of 288 relevant cases yielded follow-up data in 232 cases: Survival and mortality of group I operations are comparable to those after (extended) pneumonectomy; higher tumour stages prevailed in the combined plastic surgery subgroup. The data of group II are similar to those with lobectomy; the relatively high local recurrence rates render group II operation techniques unreliable until more data are available.

This paper quantitatively analyzes the maps of the Cancer Atlas of the Federal Republic of Germany with respect to regional clustering in the patterns of rates and relations between the patterns for different localizations. Indices of clustering and association are introduced and compared with those values resulting from computer simulations assuming random distributions. For most localizations, the clusterings could not be considered random, even though they were more or less marked, a finding which, in some cases, is neither evident nor generally known. The clusterings and correlations found offer a wealth of material for generating etiological hypotheses.

The fundamental terms in the evaluation of diagnostic tests are described and the differences to corresponding test parameters in clinical chemistry are emphasized. The derivation of a two-by two contingency table is explained in detail and basic characteristics of diagnostic tests, i.e. sensitivity and specificity as well as their independence of the prevalence (in the sense of a-priori-probability) is pointed out. The importance of the so-called predictive values is shown graphically, also the problem of selecting a cut-off-level (discrimination value) for the evaluation of quantitative data. The various attempts to find a single value for the description of a diagnostic test are discussed and it is stressed that there is no principal necessity to use other terms than those mentioned above. Nevertheless it is possible to give a prevalence-independent measure which has some additional advantages in rating and comparing simple diagnostic tests.