[Show abstract][Hide abstract] ABSTRACT: Purpose
Slipped capital femoral epiphysis (SCFE) represents the most common disorder of the hip in adolescents and a preliminary stage of degenerative joint disease. Up to now, functional outcome evaluation measured by objective instruments has been commonly neglected. The present study investigates whether the pathoanatomy of the hip joint after SCFE—analyzed on a standard X-ray—match functional results gained by three-dimensional gait analysis. A variation of functional outcome depending on the radiological findings after growth arrest is hypothesized.
Thirty-seven SCFE patients after growth arrest [mean age 18.5 years, standard deviation (SD) 4.61] with unilateral affection were included. The pathoanatomy of the hip joint was classified according to the radiological index of Heyman and Herndon and to aspherity. Three-dimensional gait analysis parameters were evaluated and subgroup analysis was performed according to the radiological results.
The radiological findings revealed very good results in general (average comprehensive index of Heyman and Herndon 94 ± 9 %, aspherity grade <2). Significant deviations of gait parameters in relation to the radiological result were an increase in step width, sagittal range of motion (ROM) of the pelvis and foot progression for the worse subgroup.
Taken as a whole, the pathoanatomy of the hip joint after SCFE matched the functional results gained by gait analysis. Functional outcome varied slightly depending on the radiological findings after growth arrest. Differences were most pronounced for foot progression. Only with the help of gait analysis was it possible to describe deviations more precisely and objectively. Further studies are required in order to show which alterations are relevant for the development of secondary osteoarthritis.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Although the survival of children and adolescents with malignant germ-cell tumours has improved greatly in recent years, the outcome remains poor for those with refractory or recurrent malignant germ-cell tumours. We aimed to determine whether objective tumour response could be achieved in patients with refractory or recurrent malignant germ-cell tumours with PEI-regional deep hyperthermia as salvage treatment.
METHODS: Patients with refractory or recurrent non-testicular malignant germ-cell tumours after standard cisplatin-based chemotherapy were treated prospectively with PEI chemotherapy (cisplatin 40 mg/m2, delivered intravenously on days 1 and 4; etoposide 100 mg/m2, intravenously on days 1-4; and ifosfamide 1800 mg/m2, intravenously on days 1-4) plus simultaneous 1-h regional deep hyperthermia (41-43°C) on days 1 and 4. Patients received three to four treatment courses at 21-day intervals until residual tumour resection was possible; they subsequently received one or two additional courses of PEI-regional deep hyperthermia. Local radiotherapy was given for incompletely resected tumours. Chemotherapy and hyperthermia toxic effects were assessed using WHO grading. The primary endpoint was the proportion of patients who had an objective response as assessed with Response Evaluation Criteria in Solid Tumors version 1.0 guidelines. Secondary endpoints were the event-free survival and overall survival after 5 years. This ongoing PEI-regional deep hyperthermia study (Hyper-PEI protocol) is registered at the German Cancer Society, number 50-2732.
FINDINGS: 44 patients aged 7 months to 21 years (median 2 years 7 months) with refractory or recurrent malignant germ-cell tumours (nine patients with poor response, 23 patients with first relapse, 12 patients with multiple relapses) were included in this study. We identified 34 yolk sac tumours, eight embryonal carcinomas, one choriocarcinoma, and one dysgerminoma by histology analysis. Of the 35 patients who had sufficient clinical and radiographical data available for response assessment, 30 (86%) had an objective response to treatment (16 patients had complete remission and 14 had partial remission). 5-year event-free survival was 62% (95% CI 45-75), and 5-year overall survival was 72% (95% CI 55-83). The median follow-up of surviving patients was 82 months (range 9-195). WHO grade 3-4 neutropenia and thrombocytopenia occurred in all 181 chemotherapy cycles. Granulocytopenic fever, which required intercurrent hospital admission, was noted in 29 (66%) of 44 patients after 53 (29%) of 181 courses. Five patients experienced treatment-related grade-3 acute renal toxic effects.
INTERPRETATION: A multimodal strategy integrating PEI-regional deep hyperthermia and tumour resection with or without radiation can successfully treat children and adolescents with refractory or recurrent malignant non-testicular germ-cell tumours. The long-term prognosis of patients with poor response or after first relapse was almost similar to those receiving first-line treatment. This strategy merits further investigation.
FUNDING: Deutsche Krebshilfe eV, Bonn, Elterninitiative Kinderkrebsklinik Düsseldorf eV, the Barbara and Hubertus-Trettnerstiftung, and the Marie Quendt Fund.
The Lancet Oncology 06/2013; · 25.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Current follow-up- and outcome-evaluations of Legg-Calvé-Perthes disease (LCPD) are based on subjective measures of function, clinical and radiological parameters. The objective of this study was to evaluate the sagittal plane kinematics and the effect on hip joint loading on the affected hip in children with LCPD.
Computerized gait analysis was performed in 49 LCPD patients aged ≥ 5 years with unilateral hip involvement. Sagittal plane kinematics and kinetics were compared to a group of healthy children (n=30).
Kinematics: a significantly increased anterior tilt and range of motion (ROM) of the pelvis combined with a marked reduction of the extension of the involved hip joint compared to the control group was observed. The increased ROM of the contralateral hip results from increased maximum flexion. Power generation: overall significantly decreased on the involved side during florid stage. Global hip function: significantly reduced hip flexor index of the involved hip; 46.2% of the patients in advanced stage, although having no significant changes in kinematics - except increased anterior pelvic tilt - had a pathologic HFI.
Sagittal plane hip function is significantly impaired in florid and advanced LCPD. The results of this study will lead to further investigations into whether this development can be prevented by conservative or operative treatment thus improving function and long-term prognosis.
[Show abstract][Hide abstract] ABSTRACT: Slipped capital femoral epiphysis (SCFE) represents the preliminary stage of osteoarthritis. Reliable tools for outcome evaluation should be developed to prevent persisting defects. The functional outcome of SCFE-patients after growth arrest is analysed by instrumented 3D-gait analysis (GA). The results are matched to the clinical examination findings.
A total of 39 SCFE patients after growth arrest (18.8 years; BMI 26.5 kg/m²) with unilateral affection were included. The clinical results were classified according to Harris hip and clinical Heyman Herndon scores. 3D-GA-parameters were evaluated and compared to the sound side and a group of 40 healthy adults (28.0 years; 21.9 kg/m²). The subgroup analysis was performed according to clinical results.
The clinical examination revealed very good results. GA could detect even small alterations. Some parameters indicated sustained functional impairments: Compared to the control group patients' walking speed (p = 0.022), step frequency (p < 0.001) and single support of the slip side (p < 0.001) decreased, while step width (p = 0.014), double support (p = 0.004) and stance time of sound side increased (p = 0.001). For kinematics patients, the sagittal range of motion (ROM) of pelvis (p < 0.001) and the external rotation of the ankle on both sides increased (p = 0.011) and sagittal ROM of hip (p = 0.002) and knee flexion of slip side (p < 0.001) decreased. The sagittal ROM of the ankle on the slip side decreased compared to the sound side (p = 0.003). Subgroup analysis revealed a positive correlation between clinically unsatisfying results and GA parameters.
Functional impairments in SCFE-patients can be found even after growth arrest. Alterations are explained partly by the disease and partly by patients' constitution. BMI-matched controls and long-term follow-up are needed.
International Orthopaedics 11/2011; 36(5):1031-8. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate the functional impairments during gait after Legg-Calvé-Perthes Disease (LCPD) and to correlate these data with the clinical and radiographic outcome.
In 13 individuals with LCPD in recovery or final stage (mean age 9.5 ± 3.5 years) with unilateral hip involvement the clinical result was graded according to Tönnis and the radiographic outcome according to Heyman and Herndon; the functional impairment during gait was compared to a group of healthy children (n = 30, mean age 8.1 ± 1.2 years). All children underwent computerised three-dimensional gait analysis.
The standard physical examination resulted in 69.2% normal range of movement according to Tönnis, but overall analysis of gait revealed that only 30.7% had a normal gait pattern. All children with an excellent or good radiographic (n = 6) outcome walked normally or showed minor deviations.
The results of the standard clinical examination do not reflect the function of the hip joint during gait. Additional information is revealed from gait analysis and should be part of outcome studies in LCPD.
International Orthopaedics 04/2011; 35(12):1833-7. · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To analyze the inquiries sent to an online ask-the-rheumatologist service in order to identify the users' needs and requirements.
The official web site of the German Competence Network Rheumatology (www.rheumanet.org) provided expert information for patients, relatives, and physicians. We analyzed the content of 1,133 inquiries posted over 5 years and the experts' answers were blinded for analyses.
Patients (60.0%), relatives (24.3%), and physicians (15.7%) addressed the experts. Inquiries were predominantly sent by women (62.2%). Distinct rheumatic diseases were mentioned in 40.5% of the inquiries, and 16.3% reported musculoskeletal symptoms without a definite diagnosis. The number of questions ranged from 1-7 per inquiry (mean±SD 1.58±0.9). Of the inquiries, 33.2% contained personal histories, 24.9% searched for a rheumatologist nearby, and 11.6% asked for a "second opinion." The questions covered a wide range of interests, including medication (30.8%), diagnosis-related issues (15.7%), laboratory tests (6.9%), (treatment) guidelines (6.2%), sexual and reproductive health issues (4.1%), and clinical trials (3.4%). In more than 50% of the inquiries, the information requested from the experts was already at least partly published on the web site. The experts' answers covered the users' questions completely in 91.8%, partly in 6.1%, and not at all in 2.1%.
A standardized medical web site providing tailored and trustworthy information for all user groups gains from an ask-the-expert service. Only such an interactive online application is able to satisfy users' actual demands: searching for specific individualized information on the internet. Therefore, an ask-the-expert service contributes to optimized patient care.
[Show abstract][Hide abstract] ABSTRACT: To determine whether MR bone marrow findings in Gaucher patients may help to identify patients at high risk of developing severe Gaucher bone complications exemplified by avascular necrosis (AVN) of the femoral head.
MR images were obtained in 63 Type I Gaucher patients through a standard protocol using coronal T 1 and T 2-weighted sequences of the lower extremities. The location and extent of infiltrated marrow was established using a semi-quantitative MRI scoring method (Düsseldorf Gaucher score, DGS) and the morphological pattern of bone marrow involvement determined (whether homogeneous type A or non-homogeneous type B). The active marrow process with bone edema and AVN of the femoral head were also analyzed.
Bone marrow involvement was observed in femoral sites more than in tibial sites. A high DGS was significantly correlated with type B morphology and femoral AVN (both p < 0.0001). Splenectomized patients showed a significantly higher Düsseldorf Gaucher score and type B morphology than non-splenectomized patients (both p < 0.05). AVN was seen in 46 % of patients with type B morphology versus 3 % in type A morphology (p < 0.0001). DGS and morphology of bone marrow involvement were not significantly correlated with active marrow processes.
Type B marrow morphology and extensive marrow packing were significantly associated with AVN of the femoral head (both p < 0.0001). These patterns are considered predictive and may be employed in a disease management context to alert physicians to the need for urgent therapeutic measures.
RöFo - Fortschritte auf dem Gebiet der R 11/2010; 182(11):979-85. · 2.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Question arises as to what extent communication skills are considered in continuing medical education (CME).
Analysis for CME-courses in communication skills in the area of the Chamber of Physicians North Rhine (ÄkNo), Germany. Supply Arm(A): CME events (n = 19,320) certified in 2007 were evaluated. Demand Arm(B): course participation of 850 family physicians in the period 2002-2007 was analyzed (n = 37,724). Tests were calculated to the level 0.05 using Mann-Whitney U-test.
(A) 388 (2.0%) events were concerned with the topic communications. 59.3% involved active cooperation of the participants. 0.5% events devoted more than 50% of their duration to the topic communication. Proportions in the subjects of internal medicine, general medicine and pediatrics amounted to 0.2%. (B) 803 (2.1%) events with a focus on communication were identified. Women took part in significantly more events than men (p<0.002) and selected more interactive courses.
Content on communication training was small. Increasing experience does not automatically improve communication skills but an extent of deliberate praxis seems to be necessary and must be sought and developed.
Communication skills are still insufficiently provided in CME-courses and should be more directed to focus as treatment strategies and scientifically investigated for outcome improvements.
Patient Education and Counseling 09/2010; 84(2):170-5. · 2.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical significance of viral load and co-infections in children with respiratory infections is not clear.
To evaluate the correlation of viral load as well as viral and bacterial co-infections with disease severity in hospitalized children with lower respiratory tract infections (LRTIs).
This is a prospective study conducted in children admitted for LRTIs for two seasons. To determine viral and bacterial load of respiratory pathogens we performed multiplex real-time polymerase chain reaction and semiquantitative bacterial cultures on nasopharyngeal aspirates (NPA).
During the study period 244 (60%) children were hospitalized for LRTI with acute virus-induced wheezing and 160 (40%) for radiologic confirmed pneumonia. In the first NPA, viruses were identified in 315 (78%) of the 404 samples and bacteria in 198 (63.3%) of 311 samples. The viral load significantly decreased between the first and second NPA sample in most single and viral co-infections, except rhinovirus and human bocavirus infections. Viral load was inversely related to CRP in RSV infections, whereas a positive correlation was observed in adenovirus infections. Duration of hospitalization was significantly longer in RSV single infections compared to rhinovirus single infections whereas in the latter, leucocytosis and use of systemic steroids was more common. In RSV viral co-infections the presence of fever, leucocytosis, and the use of antibiotics was significantly more frequent. Positive cultures of Haemophilus influenzae dominated in RSV and rhinovirus single infections and Moraxella catarrhalis in RSV viral co-infections.
Specific viral single and co-infections as well as viral load contribute to disease severity in children with LRTIs.
Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 08/2010; 48(4):239-45. · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: the study analyses the supply and the demand for Continuing Medical Education (CME) in the area served by the "Ärztekammer Nordrhein (ÄkNo)", which is one of the biggest regional Chambers of Physicians in Germany. Both the supply of all CME events certified by the ÄkNo in 2007 (n=18,932) and the participation of physicians in CME activities - using the example of family doctors (n=850), ophthalmologists (n=122) and orthopaedists (n=38) in the university towns of Cologne, Bonn and Aachen - was analysed for the period of 2002 to 2007 (n=44,760 events).
differences between groups were tested by the nonparametric Kruskal-Wallis method; adjustment for other factors was performed using Cochran-Mantel-Haenszel tests. The significance level was chosen to be 0.05.
half of the accredited CME activities had been provided in the form of lectures accompanied by discussion. This didactic focus is reflected by the CME choices of the analysed physicians, although interactive, multimedia materials and case based formats have been demonstrated to be advantageous. Family physicians and ophthalmologists participated twice as often in CME events as orthopaedists (p<0.001). Across all the disciplines investigated, female physicians participated significantly more often in CME events than their male colleagues (p<0.03).
our results show individual, group and gender specific differences in Continuing Medical Education which so far have not been adequately recognised and which warrants more research on CME.
Zeitschrift für Evidenz Fortbildung und Qualität im Gesundheitswesen 01/2010; 104(10):754-60.
[Show abstract][Hide abstract] ABSTRACT: We evaluated the feasibility of electronic data capture of self-administered patient questionnaires using a Tablet PC for integration in routine patient management; we also compared these data with results received from corresponding paper-pencil versions.
Standardised patient questionnaires (FFbH/HAQ, BASDAI, SF-36) were implemented in our documentation software. 153 outpatients (rheumatoid arthritis, systemic lupus erythematosus, spondyloarthritis) completed sets of questionnaires as paper-pencil and electronic versions using a Tablet PC. The quality and validity of data obtained using a Tablet PC and the capability of disabled patients to handle it were assigned; patients' experiences, preferences and computer/internet use were also assessed.
Scores obtained by direct data entry on the Tablet PC did not differ from the scores obtained by the paper-pencil questionnaires in the complete group and disease subgroups. No major difficulties using the Tablet PC occurred. 62.1% preferred remote data entry in the future. Seven (4.6%) patients felt uncomfortable with the Tablet PC due to their rheumatic disease.
Self-administered questionnaires via Tablet PC are a facile and capable option in patients with rheumatic diseases to monitor disease activity, efficacy and safety assessments continuously. Tablet PC applications offers directly available data for clinical decision-making improves quality of care by effective patient monitoring, and contributes to patients' empowerment.
Annals of the rheumatic diseases 12/2008; 67(12):1739-41. · 8.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Compared with conventional films digital radiography allows a wide range of exposure and scanner settings. The aim of this study was to investigate the diagnostic accuracy of the evaluation of tooth fractures depending on variations of exposure dose, scanner settings and surrounding tissues. Extracted human teeth were exposed separately and in a pig bone phantom before and after artificial fracture at 70 kV (Gendex Oralix DC) and three exposure settings using the Vistascan System I at three different resolution settings. Five dental observers evaluated 432 radiographs of 12 adequately fractured teeth under randomized conditions for the existence of a tooth fracture on a five-point scale. The highest value of true ratings (76.7%) with pig bone vicinity was achieved at 56 micro Gy (160 ms) and 20 lp mm(-1), followed by 71.7% at 27 micro Gy (80 ms) and 20 lp mm(-1). The worst diagnostic accuracy of 56.7% true ratings resulted from 6 micro Gy (20 ms) and 10 lp mm(-1). With radiographs of teeth in empty surroundings the rate of true decisions was in some cases significantly higher. For the diagnostics of tooth fractures with the Vistascan System I the diagnostic value seems to depend on, besides radiographic projection, the scanner resolution setting, the surrounding tissues and the exposure dose.
[Show abstract][Hide abstract] ABSTRACT: Switching from cyclosporine to tacrolimus without steroid pulse was suggested as a therapeutic option in chronic allograft nephropathy (CAN). Thirty-one renal transplant recipients with CAN were prospectively converted from cyclosporine to tacrolimus (group A), in parallel 31 matched cyclosporin A (CsA) patients (group B) without CAN were followed up for 30 months. In six matching patients of groups A and B inulin and para-aminohippurate (PAH)-clearances and mycophenolate were measured over a span of 3 months. Transplant biopsies of group A were scored according to BANFF. While group A presented with transplant dysfunction compared with group B before switching (2.7 +/- 0.16 mg/dl vs. 1.7 +/- 0.09 mg/dl; P < 0.001), transplant function was equal 30 months later: it ameliorated in group A (2.0 +/- 0.18 mg/dl vs. 2.7 +/- 0.16 mg/dl; P < 0.001) and decreased in group B (1.9 +/- 0.13 mg/dl vs. 1.7 +/- 0.09 mg/dl, P < 0.05). Especially, patients with biopsy scores I and II according to BANFF benefited from tacrolimus. Within 3 months, mycophenolate acid (MPA) levels increased under tacrolimus (P < 0.05) whereas inulin and PAH-clearances remained unchanged. At switching, antihypertensive treatment was more intense in group B, but this difference evened out. Adverse side effects were more frequent under tacrolimus. Patients with mild to moderate CAN significantly benefited from switching to tacrolimus. Increased MPA-levels under tacrolimus might have contributed to this effect.
Transplant International 09/2008; 21(12):1153-62. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Due to PSA screening and increased awareness, prostate cancer (PCa) is identified earlier resulting in smaller diagnostic samples on prostate needle biopsy. Because Gleason grading plays a critical role in treatment planning, we undertook a controlled study to evaluate interobserver variability among German pathologists to grade small PCas using a series of tissue microarray (TMA) images.
We have previously demonstrated excellent agreement in Gleason grading using TMAs among expert genitourinary pathologists. In the current study, we identified 331 TMA images (95% PCa and 5% benign) to be evaluated by an expert PCa pathologist and subsequently by practicing pathologists throughout Germany. The images were presented using the Bacus Webslide Browser on a CD-ROM. Evaluations were kept anonymous and participant's scoring was compared to the expert's results.
A total of 29 German pathologists analysed an average of 278 images. Mean percentage of TMA images which had been assigned the same Gleason score (GS) as done by the expert was 45.7%. GSs differed by no more than one point (+/-1) in 83.5% of the TMA samples evaluated. The respondents were able to correctly assign a GS into clinically relevant categories (i.e. <7, 7, >7) in 68.3% of cases. A total of 75.9% respondents under-graded the TMA images. Gleason grading agreement with the expert reviewer correlated with the number of biopsies evaluated by the pathologist per week. Years of diagnostic experience, self-description as a urologic pathologist or affiliation with a university hospital did not correlate with the pathologist's performance.
The vast majority of participants under-graded the small tumors. Clinically relevant GS categories were correctly assigned in 68% of cases. This raises a potentially significant problem for pathologists, who have not had as much experience evaluating small PCas.
Journal of Cancer Research and Clinical Oncology 04/2008; 134(10):1071-8. · 2.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared the detection of malignant lesions in two different methods of parametric-guided analysis to the widely used early subtraction images. The parametric colour-coded overlays were defined by the increase of signal intensity after contrast injection and the course of the time signal intensity curve. Exams of 30 patients with histopathological evidence of 32 invasive breast carcinomas were evaluated. Five hundred five areas of additional enhancing tissue were found in the early subtraction images. The sensitivity was 100 in the subtraction images and 100 and 93.8 in the parametric images, respectively, the specificity 67.5, 84.2 and 88.7, respectively. On average 4.4 ROI-measurements were needed to find the highest increase of signal intensity in the subtraction series compared to 1.9 in the parametric images. Properly selected thresholds in parametric imaging may be helpful in the differentiation of enhancing tissue. Furthermore the parametric image-guided ROI selection significantly speeds up the analysis and makes it safer as a lower rate of ROI-measurements is needed to find the strongest enhancement.
European Radiology 01/2008; 17(12):3093-9. · 4.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nerve growth factor (NGF) plays a pivotal role in cellular survival/death decisions with the low affinity receptor p75NTR predominately transmitting anti-proliferative signals. In spite of its established role in B-cell function and identification as a prognostically favourable marker in a number of malignancies, little is known about the expression pattern and prognostic significance of p75NTR in B cell precursor-acute lymphoblastic leukaemia (BCP-ALL). p75NTR expression was prospectively studied on primary ALL-blasts in a cohort of paediatric patients with common ALL (n = 86) and preB-ALL (n = 34) treated within the Co-operative study group for childhood acute lymphoblastic leukaemia (CoALL) protocol, CoALL06-97. Flow cytometric analysis showed that almost half of the patients expressed no or negligible amounts of p75NTR (<10%). The median expression in patients expressing p75NTR beyond that threshold was 49% (range 11-100%). In patients classified as low-risk at diagnosis, p75NTR expression was significantly higher than in high-risk patients (P = 0.001). Of note, p75NTR expression was lower in the 21 patients who subsequently developed relapse compared with those remaining in remission (P = 0.038). Accordingly, relapse-free survival was significantly better in patients expressing high surface p75NTR (P = 0.041). Thus, in this prospective analysis, high p75NTR expression was a strong prognostic marker that identified a group of paediatric ALL patients with favourable outcome.
British Journal of Haematology 12/2007; 139(3):450-7. · 4.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Heat shock proteins (HSPs) play an important role in the cellular response to environmental stress and exert a cytoprotective effect. Especially HSP70 is an effective inhibitor of apoptosis, suggesting a role of HSP70 in carcinogenesis and tumor progression. To explore the relevance of HSP70 in renal cell carcinomas (RCCs), we analyzed nuclear and cytoplasmic HSP70 protein expression in formalin-fixed tissue from 145 clear cell RCCs by immunohistochemistry as well as Western blot analysis. Nuclear HSP70 expression was found in all RCCs and 75% of the tumors also exhibited a cytoplasmic HSP70 staining. Importantly, RCCs showed significantly reduced cytoplasmic (p=0.001) and combined nuclear/cytoplasmic (p=0.0022) HSP70 expression when compared with their cells of origin. A significant (p=0.0176) decrease of nuclear HSP70 expression became evident from well to poorly differentiated clear cell RCCs. Quite similarly, a trend (p=0.0558) for reduced combined nuclear/cytoplasmic HSP70 expression was shown from early (pT1) to advanced (pT3) tumor stages. Nevertheless, no correlation between HSP70 expression and patients survival became evident. In conclusion, our investigation demonstrates a significant decrease of antiapoptotic HSP70 protein expression during carcinogenesis and during progression from well (G1) to poorly (G3) differentiated clear cell RCCs. Our results suggest that HSP70-mediated inhibition of apoptosis seems to be of minor importance for carcinogenesis and tumor progression in RCCs.
Histology and histopathology 11/2007; 22(10):1099-107. · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rac proteins of the Rho-like GTPase family, including the ubiquitous Rac1, the hematopoiesis-specific Rac2, and the least-characterized Rac3 play a major role in oncogenic transformation, tumor invasion and metastasis. However, the prognostic relevance of Rac expression in human tumors has not been investigated yet. In the present study, Rac protein expression was analyzed in benign secretory epithelium, high-grade prostatic intraepithelium neoplasia (HG-PIN), and prostate carcinomas of 60 R0-resected radical prostatectomy specimens by semiquantitative immunohistochemistry. Thus, Rac proteins were significantly strongly expressed in HG-PIN (P < 0.001) and prostate carcinomas (P < 0.001) when compared with benign secretory epithelium. Accordingly, all tumor tissues analyzed by isoform-specific real-time PCR (n = 7) exhibited significantly higher RNA expression levels of Rac (i.e. sum of Rac1 and Rac3 expression levels) than the respective benign counterparts (P = 0.018) and this appeared to result mainly from increased expression of the Rac3 isoform as verified by immunoblotting. Univariate analyses showed statistically significant associations of increased Rac protein expression in prostate cancer (P = 0.045), preoperative prostate-specific antigen levels (P = 0.044), pT stage (P = 0.002), and Gleason score (P = 0.001) with decreased disease-free survival (DFS). This prognostic effect of increased protein expression of Rac remained significant even in a multivariate analysis including all these four factors (relative risk = 3.22, 95% confidence interval = 1.04-10.00; P = 0.043). In conclusion, our data suggest that increased Rac protein expression in prostate cancer relative to the corresponding benign secretory epithelium is an independent predictor of decreased DFS and appears to result mainly from increased expression of the Rac3 isoform.
Endocrine Related Cancer 07/2007; 14(2):245-56. · 5.26 Impact Factor