Lymph Node Metastases in Non-Muscle Invasive Bladder Cancer are Correlated With the Number of Transurethral Resections and Tumour Upstaging at Radical Cystectomy

The first paper in this section, from Mainz, attempts to identify the clinical variables associated with the prevalence of lymph node metastases in non-muscle invasive bladder cancer. The authors found that delay in cystectomy in this potentially dangerous type of tumour is to be avoided, with a higher incidence of lymph node metastases as the number of transurethral resections increases. A paper from Austria shows that in renal carcinoma the pT1 subdivision is associated with differences in conventional histopathology and expression of biomarkers. OBJECTIVE To identify clinical variables associated with the prevalence of lymph node metastases (LNMs) in patients with non-muscle invasive tra…

Metabolic Evaluation of 94 Patients 5 to 16 Years After Ileocecal Pouch (Mainz Pouch 1) Continent Urinary Diversion

PURPOSE In continent urinary diversion metabolic disturbances may be encountered in long-term followup. We evaluated metabolic consequences in patients with a minimum followup of 5 years after Mainz pouch 1 urinary diversion.At our institution continent urinary diversion using the ileocecal segment was performed between 1983 and 1995 in 458 patients. A total of 94 patients with an ileocecal pouch for a minimum of 5 years were reevaluated for metabolic changes. Median followup was 9.0 years. Routine laboratory parameters, blood gas analysis, vitamin B12, vitamin D25, cross-laps, bone specific alkaline phosphatase, osteocalcin and propeptide of type I collagen were obtained. Bone density was …

Two-stage adaptive designs with correlated test statistics.

When performing a trial using an adaptive sequential design, it is usually assumed that the data for each stage come from different units; for example, patients. However, sometimes it is not possible to satisfy this condition or to check whether it is satisfied. In these cases, the test statistics and p-values of each stage may be dependent. In this paper we investigate the type I error of two-stage adaptive designs when the test statistics from the stages are assumed to be bivariate normal. Analytical considerations are performed under the restriction that the conditional error function is constant in the continuation region. We show that the decisions can become conservative as well as an…

Idiopathic infantile asymmetry, proposal of a measurement scale

Abstract To evaluate the development of idiopathic infantile asymmetry and the efficacy of therapeutic interventions, spinal scoliosis can be quantified on the basis of radiographs. For obvious reasons, use of this technique is limited. Here we present a clinical method to describe and quantify infantile asymmetry. For item selection, spontaneous movements (SMs), reactive movements (RMs) and length differences were video recorded in 30 infants (median age 10 weeks, range 6–16) with variable degrees of asymmetry. Within these three categories, reactive movements elicited by head turns to the right and left side in the prone and supine position emerged as reliable parameters reflecting trunk …

Adaptive designs with correlated test statistics

In clinical trials, the collected observations such as clustered data or repeated measurements are often correlated. As a consequence, test statistics in a multistage design are correlated. Adaptive designs were originally developed for independent test statistics. We present a general framework for two-stage adaptive designs with correlated test statistics. We show that the significance level for the Bauer-Köhne design is inflated for positively correlated test statistics from a bivariate normal distribution. The decision boundary for the second stage can be modified so that type one error is controlled. This general concept is expandable to other adaptive designs. In order to use these de…

Longitudinal Study on Growth and Body Mass Index before and after Diagnosis of Childhood Craniopharyngioma

Abstract We analyzed whether childhood craniopharyngioma predisposes to obesity and growth impairment. Height/length, body mass index (BMI), and hypothalamic involvement were evaluated in 90 patients at standardized ages and time points before, after, and at the time of diagnosis. Relevant decreases in height sd score (SDS) started at 10–12 months of age and persisted until diagnosis of childhood craniopharyngioma. Relevant increases in BMI SDS were detectable between 4 and 5 yr of age. Postoperative BMI SDS (yr 1–6) had a weak positive correlation with BMI SDS at the time of diagnosis. In linear regression analysis, hypothalamic tumor involvement (P < 0.001), ponderal index at birth…

Degradation of phosphatidylethanol counteracts the apparent phospholipase D-mediated formation in heart and other organs.

Phosphatidylalcohols, such as phosphatidylethanol (PEth), are formed from phosphatidylcholine in the presence of a primary alcohol (e.g., ethanol). This 'transphosphatidylation' reaction is used as specific phospholipase D (PLD) assay. Accumulation of PEth in tissues is recognized as a reliable measure of PLD activity, as PEth is allegedly metabolically stable. The general validity of this assumption was reinvestigated in isolated rat heart, small intestine and brain slices. The half-times of 3H-PEth degradation (labelled with 3H-myristic acid and preformed by ethanol exposure for 30 min) were about 1 h in heart and small intestine, but 17 h in brain. As the formation of PEth is superimpose…

Acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects.

Abstract The German MAK value of 1-methoxypropanol-2 has been fixed at 100 ppm. The aim of this study was to evaluate possible acute effects of an exposure to 100 ppm 1-methoxypropanol-2 on the upper airways of human subjects. Twenty subjects were exposed in a crossover design to 100 ppm 1-methoxypropanol-2 and to air in an exposure chamber for 4 h. Subjective symptoms were assessed by questionnaire. Olfactory thresholds for n-butanol and mucociliary transport time were measured before and after exposure. Concentrations of interleukin 1β and interleukin 8 were determined in nasal secretions taken after exposure. mRNA levels of interleukins 1β, 6 and 8, tumor necrosis factor α, granulocyte-m…

Melatonin Secretion and Increased Daytime Sleepiness in Childhood Craniopharyngioma Patients

Craniopharyngioma is a rare dysontogenetic benign tumor. Patients frequently suffer from endocrine deficiencies, sleep disturbances, and obesity due to pituitary and hypothalamic lesions. A self-assessment daytime sleepiness questionnaire (German version of the Epworth Sleepiness Scale) was used to evaluate 79 patients with childhood craniopharyngioma. Because hypothalamic lesions may explain daytime sleepiness in craniopharyngioma patients, salivary melatonin and cortisol concentrations were examined in obese and nonobese craniopharyngioma patients (n = 79), patients with hypothalamic pilocytic astrocytoma (n = 19), and control subjects (n = 30). Using a general linear model procedure anal…

An optimal code for patient identifiers.

How to distinguish 1 billion individuals by an identifier consisting of eight characters, allowing a reasonable amount of error detection or even error correction? Our solution of this problem is an optimal code over a 32-character alphabet that detects up to two errors and corrects one error as well as a transposition of two adjacent characters. The corresponding encoding and error checking algorithms are available for free; they are also embedded as components of the pseudonymisation service that is used in the TMF-the German telematics platform for health research networks.

The prognostic impact of blood group-related antigen Lewis Y and the ABH blood groups in resected non-small cell lung cancer.

The blood group antigen Lewis Y is expressed on epithelial tumors of the respiratory, digestive and reproductive system. Despite being regarded as an attractive target for immunotherapy, its function is still not well defined and its prognostic value remains a subject of discussion. Eighty-three paraffin-embedded tissue sections of non-small cell lung cancer (NSCLC) patients in stage I-IIIa, who underwent surgical resection of the primary tumor (73% male; 43% adenocarcinoma), were stained with a new, highly specific monoclonal antibody against Lewis Y (clone A70-C/C8). A positive Lewis Y expression was observed in 51% of patients; adenocarcinomas were favorably stained (67%). Multivariate a…

Bcl-2, Bcl-xl, and pp32/PHAPI in resected non-small-cell lung cancer patients

Einleitung: Fur viele Tumorarten ist der Einfluss des Apoptosesignalweges auf die Prognose der Tumorerkrankung beschrieben worden. So konnte fur die antiapoptotischen Proteine wie Bcl-2 und Bcl-xL gezeigt werden, dass sie den mitochondrialen Selbstzerstorungsmechanismus der Zellen herunterregulieren konnen. Fur nicht-kleinzellige Lungenkarzinomen (NSCLC) hingegen existieren widerspruchliche Angaben in der wissenschaftlichen Literatur in Bezug auf die prognostische Wertigkeit apoptotischer und insbesondere antiapoptotischer Faktoren. Ein weiterer wichtiger Faktor im genannten Mechanismus, welches NSCLC fur apoptotische Stimuli sensibilisieren soll, ist das Protein pp32/PHAPI. Fur bereits che…

Abstract 3463: Treatment of young children with localized medulloblastoma by chemotherapy alone: Final results of the prospective multicenter trial HIT 2000 confirming the prognostic impact of histology

Abstract Background: This study was designed to confirm the previously observed favorable survival rates and prognostic factors in young children with non-metastatic medulloblastoma (MB) treated by postoperative chemotherapy alone. Methods: Patients diagnosed between January 2001 and December 2005 and younger than 4 years received three cycles of postoperative systemic multiagent chemotherapy and intraventricular methotrexate. In case of complete remission, treatment was terminated after two additional cycles of chemotherapy. Otherwise secondary surgery, radiotherapy and consolidation chemotherapy were recommended. Results: The 5-year event-free survival (EFS) and overall survival (OS) (±SE…

An educational multimedia campaign improves stroke knowledge and risk perception in different stroke risk groups.

Background and purpose:  Stroke risk factor knowledge and individual risk perception are low in the general public. Our study aimed at identifying the educational effects of a multimedia campaign on stroke knowledge and risk perception in several subgroups at increased risk of stroke. Methods:  Telephone surveys were administered in a random sample of 500 members of the general public, before and immediately after an intense 3 months educational campaign using various mass and print media. Results:  A total of 32.7% of respondents considered themselves as being at risk of stroke before, and 41.9% (P < 0.01) after the intervention. Evaluation of stroke risk increased with number of appreciat…

Treatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters

Purpose To assess an intensified treatment in the context of clinical and biologic risk factors in metastatic medulloblastoma. Patients and Methods Patients (4 to 21 years old, diagnosed between 2001 and 2007) received induction chemotherapy, dose-escalated hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy. Subgroup status and other biologic parameters were assessed. Results In 123 eligible patients (median age, 8.2 years old; median follow-up, 5.38 years), 5-year event-free survival (EFS) and overall survival (OS) were 62% (95% CI, 52 to 72) and 74% (95% CI, 66 to 82), respectively. OS was superior compared with the precedent HIT ’91 trial. The 5-year EFS and OS wer…

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort

PURPOSE The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children &lt; 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy. PATIENTS AND METHODS From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression. After 2006, local radiotherapy was introduced for nonresponders or patients with classic medulloblastoma (CMB) or large-cell/anaplastic medulloblastoma (LCA). DNA methylation profiles of infantile sonic hedgehog-activated medulloblastoma (SHH-INF) were subdivided i…

TA-MUC1 epitope in non-small cell lung cancer

MUC1 (CD227), an established tumor marker, is expressed on glandular epithelia and on epithelial tumors. Tumor MUC1 differs from normal MUC1 by modified glycan side chains. Recently, a novel carbohydrate-induced conformational tumor-associated MUC1 epitope (TA-MUC1) was described, whose clinical relevance in lung cancer is not known. Eighty-five paraffin embedded tissue sections of non-small cell lung cancer (NSCLC) patients (73% male; mean age 64+/-9 years) were stained with the monoclonal antibody PankoMab (against TA-MUC1) and compared with the established antibodies E29 and 214D4 regarding prognostic relevance. TA-MUC1 is virtually absent in bronchial epithelium. As shown by multivariat…

Changes over three decades in outcome and the prognostic influence of age-at-diagnosis in young patients with neuroblastoma: a report from the International Neuroblastoma Risk Group Project.

Abstract Purpose Increasing age has been an adverse risk factor in children with neuroblastoma (NB) since the 1970’s, with a 12-month age-at-diagnosis cut-off for treatment stratification. Over the last 30 years, treatment intensity for children >12 months with advanced-stage disease has increased; to investigate if this strategy has improved outcome and/or reduced the prognostic influence of age, we analysed the International Neuroblastoma Risk Group (INRG) database. Patients and methods Data from 11,037 children with NB (1974–2002) from Australia, Europe, Japan, North America. Cox modelling of event-free survival (EFS) tested if the era and prognostic significance of age-of-diagnosis, adj…

Strategies for Including Patients Recruited During Interim Analysis of Clinical Trials

In clinical trials a periodical check of safety and efficacy data is often needed. For organizational reasons it is rarely desirable to stop a trial during such an interim analysis. Therefore, new study patients are included in the trial while the interim analysis is ongoing. Disregarding the additional information provided by these interim patients would be unsatisfactory, especially for an office of regulatory affairs. Consequently, the rules for group sequential or adaptive decisions must be adjusted to the recruitment of interim patients. In this paper, two strategies for modifying study designs to consider the analysis of interim patients are proposed.

MBCL-07. NON-METASTATIC MEDULLOBLASTOMA OF EARLY CHILDHOOD: RESULTS FROM THE PROSPECTIVE CLINICAL TRIAL HIT-2000 AND AN EXTENDED VALIDATION COHORT

Abstract OBJECTIVE To avoid craniospinal irradiation (CSI) in children younger than four years with non-metastatic medulloblastoma by chemotherapy, intraventricular methotrexate and risk-adapted local radiotherapy. PATIENTS AND METHODS Eighty-seven patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for non-response or progression. After 2006, local radiotherapy was introduced for non-responders or classic (CMB), anaplastic or large-cell medulloblastoma (LCA). Infantile SHH-activated medulloblastomas (SHH_INF) were subdivided by DNA-methylation profiling. Survival in SHH_INF subtypes were also assessed in a validation cohort (n=71). RESULT…

Revised risk estimation and treatment stratification of low- and intermediate-risk neuroblastoma patients by integrating clinical and molecular prognostic markers.

Abstract Purpose: To optimize neuroblastoma treatment stratification, we aimed at developing a novel risk estimation system by integrating gene expression–based classification and established prognostic markers. Experimental Design: Gene expression profiles were generated from 709 neuroblastoma specimens using customized 4 × 44 K microarrays. Classification models were built using 75 tumors with contrasting courses of disease. Validation was performed in an independent test set (n = 634) by Kaplan–Meier estimates and Cox regression analyses. Results: The best-performing classifier predicted patient outcome with an accuracy of 0.95 (sensitivity, 0.93; specificity, 0.97) in the validation coh…

Prognostic Stratification For Curatively Resected NSCLC Patients By Apoptosis Panel

The Candy Smell Test in Clinical Routine

Background The “Candy Smell Test” (CST) has been introduced as a new testing method for the evaluation of the human sense of smell. In contrast to other established orthonasal smell tests, the CST addresses the retronasal application of odors, typical for food aroma effects during mastication and swallowing. The aim of this study was to evaluate the CST in a clinical setting in patients with olfactory dysfunction and normal controls against the Sniffin’ Sticks test. Furthermore, cutoff points for normal and pathological results in the CST should be determined. Methods The olfactory performance of 96 patients presenting with olfactory disorders and 71 healthy controls was evaluated with the …

Infantile postural asymmetry and osteopathic treatment: a randomized therapeutic trial

The aim of this study was to assess the therapeutic efficacy of osteopathic treatment in infants with postural asymmetry. A randomized clinical trial of efficacy with blinded videoscoring was performed. Sixty-one infants with postural asymmetry aged 6 to 12 weeks (mean 9wks) were recruited. Thirty-two infants (18 males, 14 females) with a gestational age of at least 36 weeks were found to be eligible and randomly assigned to the intervention groups, 16 receiving osteopathic treatment and 16 sham therapy. After a treatment period of 4 weeks the outcome was measured using a standardized scale (4-24 points). With sham therapy, five infants improved (at least 3 points), eight infants were uncha…

Risk estimation in localized unresectable single copy MYCN neuroblastoma by the status of chromosomes 1p and 11q

In localized neuroblastoma, the identification of patients requiring intensive treatment is still difficult. We retrospectively analyzed data of 280 single copy MYCN stage 2 and 3 neuroblastoma patients with gross residual tumor after initial surgery. The 3-year-event free survival of the total group was 83+/-2%, and 3-year-overall survival was 92+/-2%. Patients < or=1.5 years had a better outcome than older children. Deletions/imbalances of chromosome 1p were found in 9/90 patients and were associated with a higher event rate but not with a higher death rate. Aberrations of chromosome 11q in 14/91 patients were correlated with a higher event and death rate. Multivariate analysis identified…

S36.4: Control of false discovery rate in adaptive designs

Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease?

Small cell lung cancer (SCLC) is usually classified into a two-stage system, limited (LD) and extensive disease (ED). However, the criteria for these two categories remain controversial. The widely used Veterans Administration Lung Study Group (VALG) definition of LD includes patients with primary tumor and nodal involvement limited to one hemithorax. In contrast, the International Association for the Study of Lung Cancer (IASLC) recommends that LD should additionally include all patients without distant metastasis. As a consequence, since treatment modalities for LD and ED could be different, individual clinical outcome of SCLC patients may be influenced by the staging system chosen. Among…