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1.
Strahlenther Onkol ; 190(7): 676-85, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24577133

ABSTRACT

BACKGROUND: Survival upon diagnosis of brain metastases (BM) in patients with non-small cell lung cancer (NSCLC) is highly variable and established prognostic scores do not include tissue-based parameters. METHODS: Patients who underwent neurosurgical resection as first-line therapy for newly diagnosed NSCLC BM were included. Microvascular density (MVD), Ki67 tumor cell proliferation index and hypoxia-inducible factor 1 alpha (HIF-1 alpha) index were determined by immunohistochemistry. RESULTS: NSCLC BM specimens from 230 patients (151 male, 79 female; median age 56 years; 199 nonsquamous histology) and 53/230 (23.0%) matched primary tumor samples were available. Adjuvant whole-brain radiation therapy (WBRT) was given to 153/230 (66.5%) patients after neurosurgical resection. MVD and HIF-1 alpha indices were significantly higher in BM than in matched primary tumors. In patients treated with adjuvant WBRT, low BM HIF-1 alpha expression was associated with favorable overall survival (OS), while among patients not treated with adjuvant WBRT, BM HIF-1 alpha expression did not correlate with OS. Low diagnosis-specific graded prognostic assessment score (DS-GPA), low Ki67 index, high MVD, low HIF-1 alpha index and administration of adjuvant WBRT were independently associated with favorable OS. Incorporation of tissue-based parameters into the commonly used DS-GPA allowed refined discrimination of prognostic subgroups. CONCLUSION: Ki67 index, MVD and HIF-1 alpha index have promising prognostic value in BM and should be validated in further studies.


Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/secondary , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Ki-67 Antigen/metabolism , Microvessels/pathology , Brain Neoplasms/diagnosis , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Brain Neoplasms/therapy , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , Female , Humans , Male , Middle Aged , Prevalence , Prognosis , Reproducibility of Results , Risk Factors , Sensitivity and Specificity , Survival Analysis
2.
Eur Respir J ; 37(5): 1096-103, 2011 May.
Article in English | MEDLINE | ID: mdl-20693249

ABSTRACT

Current guidelines recommend right heart catheterisation (RHC) in symptomatic patients at risk of pre-capillary pulmonary hypertension (PH) with echocardiographic systolic pulmonary artery pressures ≥ 36 mmHg. Growing awareness for PH, a high prevalence of post-capillary PH and the inability to distinguish between pre- and post-capillary PH by echocardiography have led to unnecessary RHCs. The aim of our study was to assess whether standard noninvasive diagnostic procedures are able to safely exclude pre-capillary PH. Data from 251 patients referred for suspicion of pre-capillary PH were used to develop a noninvasive diagnostic decision tree. A prospectively collected data set of 121 consecutive patients was utilised for temporal validation. According to the decision tree, patients were stratified by the presence or absence of an electrocardiographic right ventricular strain pattern (RVS) and serum N-terminal brain natriuretic peptide (NT-proBNP) levels below and above 80 pg·mL⁻¹. In the absence of RVS and elevated NT-proBNP, none of the patients in the prospective validation cohort were diagnosed with pre-capillary PH by RHC. Combining echocardiography with the diagnostic algorithm increased specificity to 19.3% (p = 0.0009), while sensitivity remained at 100%. Employing ECG and NT-proBNP on top of echocardiography helps recognise one false positive case per five patients referred with dyspnoea and echocardiographic suspicion of PH, while not missing true pre-capillary PH.


Subject(s)
Algorithms , Cardiac Catheterization , Hypertension, Pulmonary/diagnosis , Adult , Aged , Cohort Studies , Electrocardiography/methods , Female , Heart Ventricles/diagnostic imaging , Heart Ventricles/physiopathology , Humans , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/physiopathology , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Prospective Studies , Retrospective Studies , Sensitivity and Specificity , Ultrasonography
3.
Ann Rheum Dis ; 69(1): 169-74, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19153104

ABSTRACT

OBJECTIVE: To investigate time courses of autoantibody profiles in patients with early arthritis. PATIENTS AND METHODS: A total of 200 patients with very early arthritis (<3 months duration), among them 102 patients with a final diagnosis of rheumatoid arthritis (RA) and 98 with other rheumatic diseases, were followed up for several years. First follow-up testing was performed in all patients (mean 5 months from baseline), and 82 patients with RA and 35 patients without RA were available for last follow-up testing (mean 32 months from baseline). IgM-rheumatoid factor (RF) was measured by nephelometry, IgA-RF, IgG-RF and anti-cyclic citrullinated peptide antibodies (ACPA) by ELISA, and anti-RA33 antibodies were determined by immunoblotting. RESULTS: At baseline, IgA-RF was detectable in 29% and IgG-RF in 14% of patients with RA while IgM-RF>50 IU/ml (RF50) was positive in 45% of the patients; specificities were 97%, 99% and 96%, respectively. However, the vast majority of patients positive for IgA-RF or IgG-RF were also positive for RF50 or ACPA. During follow-up, the prevalence of ACPA slightly increased while prevalence of all RF subtypes and anti-RA33 decreased. Remarkably, the number of patients positive for RF50 and/or ACPA remained constant, and these patients had a highly increased risk for developing erosive disease in contrast to patients solely positive for anti-RA33. CONCLUSIONS: Testing for RF subtypes did not provide additional diagnostic information. Patients positive for RF50 and/or ACPA had an unfavourable prognosis, irrespectively of changes in the antibody profile during follow-up, whereas anti-RA33 positivity was inversely associated with erosiveness at baseline and at later time points.


Subject(s)
Arthritis, Rheumatoid/immunology , Autoantibodies/blood , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Antinuclear/blood , Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , Disease Progression , Female , Follow-Up Studies , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/immunology , Humans , Immunoglobulin M/blood , Male , Middle Aged , Peptides, Cyclic/immunology , Prognosis , Rheumatoid Factor/blood , Young Adult
4.
Clin Neuropathol ; 29(1): 41-54, 2010.
Article in English | MEDLINE | ID: mdl-20040333

ABSTRACT

Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.


Subject(s)
Biomarkers/metabolism , Brain Neoplasms/diagnosis , Brain Neoplasms/metabolism , Translational Research, Biomedical/methods , Brain Neoplasms/pathology , Education/methods , Humans , International Cooperation , Prognosis
5.
Eur J Neurol ; 16(7): 874-8, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19473360

ABSTRACT

BACKGROUND: Peritumoral brain edema in glioblastoma patients is a frequently encountered phenomenon that strongly contributes to neurological signs and symptoms. The role of peritumoral edema as a prognostic factor is controversial. MATERIALS AND METHODS: This multi-centre clinical retrospective study included 110 patients with histologically proven glioblastoma. The prognostic impact on overall survival of pre-treatment peritumoral edema detected on MRI-scans was evaluated. All patients had preoperative MRI, surgery, histology, and received standard treatment regimens. Edema on MRI-scans was classified as minor (<1 cm), and major (>1 cm). RESULTS: Our results confirm that peritumoral edema on preoperative MRI is an independent prognostic factor in addition to postoperative Karnofsky performance score (KPS), age, and type of tumor resection. Patients with major edema had significant shorter overall survival compared to patients with minor edema. CONCLUSION: This easily applicable early radiological characterization may contribute to a more subgroup oriented treatment in glioblastoma patients for future trials, as well as in clinical routine.


Subject(s)
Brain Edema/pathology , Brain Neoplasms/diagnosis , Glioblastoma/complications , Glioblastoma/diagnosis , Magnetic Resonance Imaging/methods , Adult , Aged , Aged, 80 and over , Brain Edema/etiology , Brain Edema/mortality , Brain Mapping , Brain Neoplasms/complications , Brain Neoplasms/mortality , Confidence Intervals , Female , Glioblastoma/mortality , Humans , Kaplan-Meier Estimate , Karnofsky Performance Status , Male , Middle Aged , Odds Ratio
6.
Histopathology ; 53(1): 39-47, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18613924

ABSTRACT

AIMS: The Ki67 tumour cell proliferation index is an independent prognostic factor in ependymoma patients. Essential prerequisites for validation of the Ki67 index as a histopathological biomarker are the reproducibility of this factor and its prognostic influence by different observers (proof of objective clinical and analytical performance). To this end, the aim was to analyse systematically inter- and intraobserver agreement and reproducibility of the prognostic impact of the Ki67 index in intracranial ependymoma. METHODS AND RESULTS: The study cohort contained 78 cases of intracranial ependymoma. In all cases, the Ki67 index was assessed by four experienced observers (EOs) and by four inexperienced observers (IOs) using the manual hot-spot method. There was considerable agreement on Ki67 index assessment. There was higher observer agreement among EOs compared with IOs. For each observer, survival analysis showed significant association of low Ki67 index with favourable patient outcome. CONCLUSIONS: Our data show that the Ki67 index in intracranial ependymoma is a reproducible and robust prognostic factor and can be considered a promising histopathological candidate biomarker. Attainment of biomarker status requires further translational studies in the context of prospective therapeutic trials.


Subject(s)
Biomarkers, Tumor/analysis , Brain Neoplasms/chemistry , Brain Neoplasms/pathology , Ependymoma/chemistry , Ependymoma/pathology , Ki-67 Antigen/analysis , Adolescent , Adult , Aged , Brain Neoplasms/mortality , Cell Count , Cell Proliferation , Child , Child, Preschool , Ependymoma/mortality , Humans , Immunohistochemistry , Infant , Middle Aged , Observer Variation , Prognosis , Reproducibility of Results , Retrospective Studies
7.
Methods Inf Med ; 46(6): 655-61, 2007.
Article in English | MEDLINE | ID: mdl-18066415

ABSTRACT

OBJECTIVES: Numerous sample size calculation programs are available nowadays. They include both commercial products as well as public domain and open source applications. We propose modifications for these programs in order to even better support statistical consultation during the planning stage of a two-armed clinical trial. METHODS: Directional two-sided tests are commonly used for two-armed clinical trials. This may lead to a non-negligible Type III error risk in a severely underpowered study. In the case of a reasonably sized study the question for the so-called auxiliary alternative may evolve. RESULTS: We propose that sample size calculation programs should be able to compute i) Type III errors and the so-called q-values, ii) minimum sample sizes required to keep the q-values below pre-specified levels, and iii) detectable effect sizes of the so-called auxiliary alternatives. CONCLUSIONS: Proposals i and ii are intended to help prevent irresponsibly underpowered clinical trials, whereas the proposal iii is meant as additional assistance for the planning of reasonably sized clinical trials.


Subject(s)
Clinical Trials as Topic/methods , Data Interpretation, Statistical , Sample Size , Software , Humans , Models, Statistical , Models, Theoretical
8.
Eur J Cancer ; 42(17): 2996-3003, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16996732

ABSTRACT

Standard postoperative treatment of medulloblastoma consists of craniospinal irradiation and chemotherapy. Currently, only clinical factors are used for therapy stratification. To optimise treatment and patient outcome, biological prognostic markers are needed. In the present study we tested the prognostic influence of four histopathological parameters considered in recent publications as prognostic factors in medulloblastoma. We analysed a series of 82 Austrian medulloblastoma patients who were treated according to the consecutive HIT protocols for medulloblastoma conducted by the German Society of Paediatric Haematology and Oncology. Histological subtype and immunohistochemical expression of erbB-2, TRKC, and survivin were determined on paraffin embedded tumour tissue and correlated with patient outcome. Statistical analysis showed a significant correlation of high expression levels of survivin with decreased survival. None of the other investigated histopathological factors correlated significantly with patient outcome. Our data indicate that high survivin expression is related to unfavourable clinical outcome in medulloblastoma patients.


Subject(s)
Cerebellar Neoplasms/pathology , Medulloblastoma/pathology , Microtubule-Associated Proteins/metabolism , Neoplasm Proteins/metabolism , Adolescent , Adult , Cerebellar Neoplasms/mortality , Child , Child, Preschool , Female , Humans , Immunohistochemistry , Infant , Infant, Newborn , Inhibitor of Apoptosis Proteins , Male , Medulloblastoma/mortality , Prognosis , Receptor, ErbB-2/metabolism , Receptor, trkC/metabolism , Survival Analysis , Survivin
9.
Leukemia ; 14(1): 68-76, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10637479

ABSTRACT

To compare the clinical relevance of drug resistance factors in de novo acute myeloid leukemia (AML), we determined their relationship to both response to induction chemotherapy and survival of the patients in univariate as well as multivariate analyses. The drug resistance factors immunocytochemically studied in 111 patients at the time of diagnosis included the lung resistance protein (LRP), P-glycoprotein (P-gp), multidrug resistance protein (MRP1) and bcl-2. In the univariate analyses, age (P = 0.005), karyotype (P = 0.03), LRP (P = 0.003), P-gp (P = 0.02) and bcl-2 (P = 0.03) predicted for response to induction chemotherapy, whereas MRP1 had no predictive value. Age (P = 0.05), karyotype (P = 0.05) and LRP (P = 0.03) retained their predictive value in the multivariate logistic regression analyses. With regard to overall survival, age (P = 0. 008), karyotype (P = 0.006), LRP (P = 0.001) and P-gp (P = 0.01) were of prognostic value in the univariate Cox regression analyses but only age (P = 0.01), karyotype (P = 0.02) and LRP (P = 0.01) retained their prognostic significance in the multivariate analyses. A risk score based on the number of independent prognostic factors allowed division of patients into four groups with different outcome. In these groups, the complete remission rates were 93%, 75%, 47% and 33%, respectively, and median overall survival was 2.4, 1.2, 0.6 and 0.2 years, respectively. Thus, several drug resistance factors did predict outcome in the univariate analyses but LRP was the only drug resistance factor with independent predictive and prognostic significance. The proposed risk score might be useful for risk-adapted treatment in the future. Leukemia (2000) 14, 68-76.


Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Myeloid/drug therapy , Acute Disease , Adolescent , Adult , Aged , Aged, 80 and over , Drug Resistance, Neoplasm/genetics , Female , Humans , Immunohistochemistry , Karyotyping , Leukemia, Myeloid/genetics , Male , Middle Aged , Survival Analysis
10.
Clin Cancer Res ; 6(9): 3417-23, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10999723

ABSTRACT

Drug resistance of non-Hodgkin's lymphomas may involve mechanisms of the multidrug resistance phenotype including the lung resistance protein (LRP) and the multidrug resistance protein (MRP1). To determine the clinical relevance of these multidrug resistance factors in previously untreated diffuse large B-cell lymphomas (n = 48), we studied LRP and MRP1 expression in lymphoma cells and their impact on clinical outcome. LRP and MRP1 expression were immunohistochemically assessed by means of the monoclonal antibodies LRP-56 and MRPr1, respectively. LRP was positive in 23% and MRP1 in 44% of the samples. LRP expression was associated with higher tumor stage (P = 0.03), elevated serum lactate dehydrogenase levels (P = 0.01), and the International Prognostic Index (P = 0.0001). LRP-positive patients had a lower complete response rate to polychemotherapy than LRP-negative patients (18 versus 65%; P = 0.006). Patients with LRP expression had a shorter overall survival than those without LRP expression (median of 0.9 years versus median not reached; P = 0.001). MRP1 expression was independent of clinical and laboratory parameters and had no impact on the outcome of chemotherapy or survival of the patients. These data suggest that LRP expression but not MRP1 expression is an important mechanism of drug resistance associated with worse clinical outcome in previously untreated diffuse large B-cell lymphomas. Thus, the reversal of LRP-mediated drug resistance may improve clinical outcome in diffuse large B-cell lymphoma in the future.


Subject(s)
ATP-Binding Cassette Transporters/biosynthesis , Lymphoma, B-Cell/drug therapy , Lymphoma, B-Cell/metabolism , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/metabolism , Neoplasm Proteins/biosynthesis , Vault Ribonucleoprotein Particles/biosynthesis , Analysis of Variance , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/administration & dosage , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Doxorubicin/administration & dosage , Drug Resistance, Multiple , Etoposide/administration & dosage , Female , Humans , Immunohistochemistry , Lomustine/administration & dosage , Male , Methotrexate/administration & dosage , Middle Aged , Multidrug Resistance-Associated Proteins , Prednimustine/administration & dosage , Prednisone/administration & dosage , Regression Analysis , Survival Analysis , Treatment Outcome , Vincristine/administration & dosage
11.
Eur J Cancer ; 32A(11): 2023-5, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8943691

ABSTRACT

We investigated the expression of CD44 isoforms containing variant exons v5, v6 and v7-8 in 115 human breast cancer specimens by means of immunohistochemistry. CD44 isoforms CD44v5, CD44v6 and CD44v7-8 were detected in 56% (n = 64), 24% (n = 28) and 15% (n = 17), respectively. In 36 specimens of axillary lymph node metastasis, expression of CD44v5, CD44v6 and CD44v7-8 was found in 94% (n = 34), 92% (n = 33) and 89% (n = 32), respectively. Five year survival rates with or without CD44v5 and CD44v6 expression were 71% versus 86% (log-rank test, P = 0.02) and 62% versus 81% (log-rank test, P = 0.001), respectively. For disease-free survival, expression of CD44v5, CD44v6 and CD44v7-8 showed a prognostic impact (log-rank test, P = 0.004, P = 0.0001 and P = 0.0001, respectively). However, multivariate analysis revealed that all investigated CD44 isoforms failed to be independent predictors of the patient's outcome.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Hyaluronan Receptors/analysis , Adult , Aged , Aged, 80 and over , Axilla , Breast Neoplasms/pathology , Female , Follow-Up Studies , Humans , Immunohistochemistry , Lymphatic Metastasis , Middle Aged , Multivariate Analysis , Prognosis , Random Allocation
12.
J Histochem Cytochem ; 46(8): 901-10, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9671441

ABSTRACT

Carbocyanines (DiI, DiA, DiO) are able to travel along membranes by diffusion and therefore have been used as postmortem neuronal tracers in aldehyde-fixed tissues. Surprisingly, detailed data on the influence of different parameters on tracing distances are still missing. This study was carried out to optimize tracing procedures and to reveal the validity of the combination of postmortem tracing with immunocytochemistry. Carbocyanine crystals were applied to the cervical spinal cord, sciatic nerves, and brachial plexuses of humans and guinea pigs. Incubation in the dark at 37C for 12-15 weeks proved optimal to achieve longest tracing distances (28.9 +/- 2.2 mm) in human and animal tissues. Longer incubation times and incubation temperatures higher than 37C did not result in longer tracing distances. No differences were evident between adult and newborn animals and between central and peripheral nervous system. The diffusion coefficient for DiI was calculated to be 2.5 x 10(-7) cm2 sec-1. After application of DiI to nerves of guinea pig extraocular muscles, DiI-positive afferent perikarya were observed in the anteromedial part of the trigeminal ganglion. These perikarya were identified by calcitonin gene-related peptide immunoreactivity (CGRP-IR). The percentage of CGRP-IR neurons after tracing was concordant with the percentage of CGRP-IR in trigeminal ganglia exclusively processed for CGRP-IR without previous postmortem tracing. These results demonstrate carbocyanines to be specific tracers for exact neuronal mapping studies. (J Histochem Cytochem 46:901-910, 1998)


Subject(s)
Carbocyanines , Coloring Agents , Neurons/cytology , Aged , Aged, 80 and over , Animals , Animals, Newborn , Cadaver , Central Nervous System/cytology , Guinea Pigs , Humans , Immunohistochemistry , Middle Aged , Neurons, Afferent/cytology , Organ Specificity , Peripheral Nervous System/cytology
13.
Invest Ophthalmol Vis Sci ; 35(13): 4317-27, 1994 Dec.
Article in English | MEDLINE | ID: mdl-8002252

ABSTRACT

PURPOSE: To examine the number and distribution of muscle spindles in all extraocular muscles (EOMs) in humans. METHODS: Thirty-six EOMs were obtained after death from three persons 67, 72, and 83 years of age. Serial sections were made throughout the length of these muscles. Consecutive sections were stained with different methods. To discriminate true spindles from false spindles, light microscopic criteria were defined and were subject to ultrastructural investigation. A distal portion of a single EOM was gained from a multiorgan donor 17 years of age, processed for electron microscopy, and analyzed. RESULTS: Spindles were observed in all muscles studied, with the medial rectus exhibiting a mean of 18.8 spindles +/- 3.0 (+/- standard deviation), the lateral rectus 19.3 +/- 1.9, the superior rectus 15.8 +/- 2.5, the inferior rectus 34.0 +/- 4.4, , the superior oblique 27.3 +/- 8.2, and the inferior oblique 4.3 +/- 1.8 per muscle [corrected]. For each different human EOM, a typical distribution of spindles was observed in the persons examined. The ultrastructural investigation revealed sensory endings in structures primarily identified as spindles. CONCLUSIONS: By comparing 1 g of tissue, spindles are found to be at least as frequent in human EOM as in skeletal muscles known to have a high density of spindles. This fact and the peculiar distribution of spindles in human EOMs suggest that spindles are functionally important proprioceptors in EOM.


Subject(s)
Muscle Spindles/ultrastructure , Oculomotor Muscles/ultrastructure , Adolescent , Aged , Aged, 80 and over , Cell Count , Eye Movements , Humans , Immunoenzyme Techniques , Proprioception
14.
Cancer Lett ; 110(1-2): 145-8, 1996 Dec 20.
Article in English | MEDLINE | ID: mdl-9018093

ABSTRACT

The influence of menstrual status at the time of surgery on the prognosis of women suffering from breast cancer is still discussed controversially. In our patient collective, including 149 patients, we obtained statistically significant results for six different time intervals, indicating that patients who underwent surgery between 11 and 22 days after the last menstrual period (LMP) have a poorer outcome. Focusing on the effect of statistical data evaluation strategy we designed a simulation study to evaluate the amount of type I error (error of a false positive test result) in a multiple testing situation involving a cyclical covariate. Accordingly, we corrected the minimum P-values for the occurring type I error rates. After that correction all six previously significant P-values failed to achieve statistical significance. The impact of different statistical data evaluation strategies in a multiple testing situation is discussed.


Subject(s)
Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , Carcinoma, Lobular/surgery , Menstrual Cycle , Adult , Data Interpretation, Statistical , Disease-Free Survival , Female , Follow-Up Studies , Humans , Middle Aged , Retrospective Studies
15.
Radiother Oncol ; 55(2): 135-44, 2000 May.
Article in English | MEDLINE | ID: mdl-10799725

ABSTRACT

BACKGROUND AND PURPOSE: To evaluate prospectively local tumor control and morbidity after 1-3 fractions of stereotactic external beam irradiation (SEBI) in patients with uveal melanoma, unsuitable for ruthenium-106 brachytherapy or local resection. MATERIAL AND METHODS: This phase I/II study includes 62 selected patients with uveal melanoma. The mean initial tumor height was 7.8+/-2.8 mm. With the Leskell gamma knife SEBI, 41 patients (66%) were irradiated with two equal fractions of 35, 30 or 25 Gy/fraction, 14 patients (22%) were treated with three fractions of 15 Gy each, and seven patients (11%) with small tumor volumes below 400 mm(3) were treated with one fraction of 45 Gy. The mean total dose was 54+/-8 Gy. The minimal follow-up period was 12 months, and the median follow-up was 28.3 months. Data on radiation-induced side-effects were analyzed with the Cox proportional hazards model for possible risk factors. RESULTS: Local tumor control was achieved in 98% and tumor height reduction in 97%. The mean relative tumor volume reductions were 44, 60 and 72% after 12, 24 and 36 months, respectively. Seven patients developed metastases (11%). Secondary enucleation was performed in eight eyes (13%). Morbidity was significant in tumors exceeding 8 mm in initial height; it was comparable and acceptable in those smaller. In the stepwise multiple Cox model, tumor localization, height and volume, planning target volume (PTV), total dose and patient age were identified as the strongest risk factors for radiation-induced lens opacities, secondary glaucoma, uveitis, eyelash loss and exudative retinal detachment. In this model, the high-dose volume irradiated with more than 10 Gy/fraction was the strongest risk factor for radiation-induced uveitis. CONCLUSIONS: Stereotactic external photon beam irradiation and a total dose of 45-70 Gy delivered in one to three fractions are highly effective at achieving local tumor control in uveal melanoma. Further clinical studies using smaller fraction doses, and consequent smaller high-dose volumes, are justified to optimize dose and fractionation. Fractionated stereotactic irradiation has a challenging potential as an eye-preserving treatment in uveal melanoma.


Subject(s)
Melanoma/surgery , Radiosurgery , Uveal Neoplasms/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Radiosurgery/adverse effects , Risk Factors
16.
J Clin Epidemiol ; 54(1): 99-103, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11165473

ABSTRACT

The aim of many epidemiological studies is the regression of a dichotomous outcome (e.g., death or affection by a certain disease) on prognostic covariables. Thereby the Poisson regression model is often used alternatively to the logistic regression model. Modelling the number of events and individual outcomes, respectively, both models lead to nearly the same results concerning the parameter estimates and their significances. However, when calculating the proportion of explained variation, quantified by an R2 measure, a large difference between both models usually occurs. We illustrate this difference by an example and explain it with theoretical arguments. We conclude, the R2 measure of the Poisson regression quantifies the predictability of event rates, but it is not adequate to quantify the predictability of the outcome of individual observations.


Subject(s)
Data Interpretation, Statistical , Epidemiologic Methods , Linear Models , Logistic Models , Poisson Distribution , Adult , Age Distribution , Aged , Aged, 80 and over , Analysis of Variance , Coronary Disease/etiology , Coronary Disease/mortality , Follow-Up Studies , Humans , Likelihood Functions , Male , Middle Aged , Predictive Value of Tests , Prognosis , Risk Factors , Smoking/adverse effects , United Kingdom/epidemiology
17.
Am J Clin Pathol ; 105(6): 705-10, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8659444

ABSTRACT

Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is reported to be an independent prognostic factor. The established method of enumeration of microvessel density is to count the vessels using an ocular raster (counted microvessel density [CMVD]). The vessels were detected by staining endothelial cells using Factor VIII-related antigen. The aim of the study was to compare the CMVD results with the percentage of factor VIII-related antigen-stained area using computer-assisted image analysis. A true color red-green-blue (RGB) image analyzer based on a morphologically reduced instruction set computer processor was used to evaluate the area of stained endothelial cells. Sixty invasive breast carcinomas were included in the analysis. There was no significant correlation between the CMVD and the percentage of factor VIII-related antigen-stained area (Spearman correlation coefficient = 0.24, confidence interval = 0.02-0.46). Although high CMVD was significantly correlated with poorer recurrence free survival (P = .024), percentage of factor VIII-related antigen-stained area showed no prognostic value. Counted microvessel density and percentage of factor VIII-related antigen-stained area showed a highly significant correlation with vessel invasion (P = .0001 and P = .02, respectively). There was no correlation between CMVD and percentage of factor VIII-related antigen-stained area with other prognostic factors. In contrast to the CMVD within malignant tissue, the percentage of factor VIII-related antigen-stained area is not suitable as an indicator of prognosis in breast cancer patients.


Subject(s)
Breast Neoplasms/chemistry , Carcinoma/chemistry , Image Processing, Computer-Assisted/methods , von Willebrand Factor/analysis , Breast Neoplasms/blood supply , Carcinoma/blood supply , Female , Humans , Image Processing, Computer-Assisted/instrumentation , Image Processing, Computer-Assisted/statistics & numerical data , Immunohistochemistry , Microcirculation/chemistry , Microcirculation/pathology , Neovascularization, Pathologic/pathology , Prognosis
18.
Obstet Gynecol ; 92(6): 967-71, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9840559

ABSTRACT

OBJECTIVE: To determine whether delayed laparotomy after attempted laparoscopic excision of an ovarian mass later found to be malignant has an impact on the stage of disease. METHODS: A questionnaire regarding laparoscopic management of ovarian masses later found to be malignant was mailed to all gynecologic departments in Austria. Of the 70 cases reported, laparotomy was performed after laparoscopy in 48 cases. In 24 of these cases, laparotomy was performed within 17 days of laparoscopy, whereas 24 cases involved a delay of more than 17 days. Twenty-two patients in whom laparotomy was performed immediately after laparoscopy were used as controls. RESULTS: In patients with borderline tumors who underwent laparotomy more than 17 days after laparoscopy, the odds ratio (OR) for International Federation of Gynecology and Obstetrics (FIGO) stage IIB-IV disease was 5.3 (95% confidence interval [CI] 0.40, infinity), compared with patients undergoing immediate laparotomy (multivariate analysis). Patients with invasive ovarian cancer who underwent laparotomy more than 17 days after laparoscopy had an OR of 9.2 (CI 0.92, 481) for stage IIB-IV disease compared with patients undergoing immediate laparotomy (multivariate analysis). In patients with borderline tumors, multivariate analysis showed that the timing of laparotomy is an independent prognostic factor for the stage of disease. In invasive ovarian cancer, none of the factors evaluated by multivariate analysis was found to be an independent prognostic factor for the distribution of disease stage. A delay between laparoscopy and laparotomy may affect adversely the distribution of disease stage. CONCLUSION: The timing of subsequent laparotomy was found to be a factor predictive of the distribution of disease stage.


Subject(s)
Laparoscopy , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Adolescent , Adult , Aged , Diagnosis, Differential , Female , Humans , Laparotomy , Middle Aged , Multivariate Analysis , Neoplasm Staging , Surveys and Questionnaires , Time Factors
19.
Obstet Gynecol ; 92(2): 245-8, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9699760

ABSTRACT

OBJECTIVE: To measure the serum levels of interleukin (IL)-8, prostaglandin (PG) F2alpha, and beta-endorphin in parturients with acupuncture treatment and in controls to clarify the effect of acupuncture and duration of labor on the serum levels of substances active in cervical ripening and dilatation. METHODS: A matched pair study was performed involving 80 women with and without prenatal acupuncture treatment, matched for age and parity. Serum levels of IL-8, PGF2alpha, and beta-endorphin were measured in serum samples taken after delivery by use of enzyme-linked immunosorbent assay, enzyme immunoassay, and immunoradiometric assay, respectively. RESULTS: The mean difference in total duration of labor between matched pairs with and without acupuncture was -136.5 minutes (95% confidence interval [CI] 191.1 minutes, -81.9 minutes; paired t test, P < .001). The mean difference of the duration of the first and second stages of labor between matched pairs with and without acupuncture was -138.8 minutes (95% CI 188.6, -89.0 minutes; paired t test, P < .001) and 2.3 minutes (95% CI 15.5, 20.1 minutes; paired t test, P = .8), respectively. The geometric means of ratios of IL-8, PGF2alpha, and beta-endorphin between matched pairs in women with and without acupuncture showed no statistically significant differences. Serum levels of IL-8, PGF2alpha, and beta-endorphin were not significantly correlated with the duration of the first and second stages of labor. CONCLUSION: Prenatal acupuncture treatment significantly reduces the duration of labor and may be a valuable tool in prenatal preparation. Serum levels of IL-8, PGF2alpha, and beta-endorphin are not significantly influenced by acupuncture and are therefore not likely to mediate acupuncture-related effects during labor.


Subject(s)
Acupuncture Analgesia , Dinoprost/blood , Interleukin-8/blood , Labor, Obstetric/blood , beta-Endorphin/blood , Adult , Female , Humans , Pregnancy , Time Factors
20.
Urology ; 52(6): 1113-7, 1998 Dec.
Article in English | MEDLINE | ID: mdl-9836565

ABSTRACT

OBJECTIVES: To measure the pressure profiles at different positions of the urethral circumference simultaneously. METHODS: Twenty-two women with symptoms of genuine stress incontinence underwent urogynecologic assessment and multichannel urethral pressure profilometry (UPP) at rest with a specially designed 8-channel urethral catheter with radial openings. RESULTS: The distribution pattern of maximum urethral closure pressure (MUCP) and functional urethral length (FUL) values were significantly different (P=0.004 and P=0.0004, respectively). Most of the highest MUCP values per patient were found between channels 2 and 4 (P=0.015); most of the greatest FUL values per patient were found between channels 3 and 4 (P=0.15). CONCLUSIONS: The data of our study substantiate asymmetric radial pressure distribution within the urethra and underline the necessity of cautious interpretation of results of conventional single-channel UPP, which might vary because of transducer orientation.


Subject(s)
Urethra/physiopathology , Urinary Catheterization/instrumentation , Urinary Incontinence, Stress/physiopathology , Urodynamics , Female , Humans , Pressure , Prospective Studies
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