Midregional proatrial naturetic peptide (MRproANP) and copeptin (COPAVP) as predictors of all-cause mortality in recently diagnosed mild to moderate COPD-results from COSYCONET.

BACKGROUND: MRproANP and COPAVP are prognostic markers for mortality in chronic obstructive pulmonary disease (COPD). Furthermore, these biomarkers predict mortality due to cardiovascular diseases, which are important prognostically determining comorbidities in patients with COPD. However, less is known about these biomarkers in recently diagnosed mild to moderate COPD. Therefore, we analyzed these biomarkers as potential predictors of mortality in recently diagnosed mild to moderate COPD. METHODS: The blood biomarkers considered were copeptin (COPAVP), midregional adrenomedullin (MRproADM), midregional proatrial naturetic peptide (MRproANP), and fibrinogen. Analyses were performed in patients with stable "recently diagnosed mild to moderate COPD" defined by GOLD grades 0-2 and diagnosis of COPD ≤ 5 years prior to inclusion into the COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network), using Cox regression analysis with stepwise adjustment for multiple COPD characteristics, comorbidities, troponin and NT-proBNP. RESULTS: 655 patients with recently diagnosed mild to moderate COPD were included. In the initial regression model, 43 of 655 patients died during the 6-year follow-up, in the final model 27 of 487. Regression analyses with adjustment for confounders identified COPAVP and MRproANP as statistically robust biomarkers (p < 0.05 each) of all-cause mortality, while MRproADM and fibrinogen were not. The fourth quartile of MRproANP (97 pmol/L) was associated with a hazard ratio of 4.5 (95%CI: 1.6; 12.8), and the fourth quartile of COPAVP (9.2 pmol/L) with 3.0 (1.1; 8.0). The results for MRproANP were confirmed in the total cohort of grade 0-4 (n = 1470 finally). CONCLUSION: In patients with recently diagnosed mild to moderate COPD, elevated values of COPVP and in particular MRproANP were robust, independent biomarkers for all-cause mortality risk after adjustment for multiple other factors. This suggests that these markers might be considered in the risk assessment of early COPD.

Interplay of tau and functional network connectivity in progressive supranuclear palsy: a [18F]PI-2620 PET/MRI study.

PURPOSE: Progressive supranuclear palsy (PSP) is primary 4-repeat tauopathy. Evidence spanning from imaging studies indicate aberrant connectivity in PSPs. Our goal was to assess functional connectivity network alterations in PSP patients and the potential link between regional tau-burden and network-level functional connectivity using the next-generation tau PET tracer [18F]PI-2620 and resting-state functional MRI (fMRI). MATERIAL AND METHODS: Twenty-four probable PSP patients (70.9 ± 6.9 years, 13 female), including 14 Richardson syndrome (RS) and 10 non-RS phenotypes, underwent [18F]PI-2620 PET/MRI imaging. Distribution volume ratios (DVRs) were estimated using non-invasive pharmacokinetic modeling. Resting-state fMRI was also acquired in these patients as well as in thirteen older non-AD MCI reference group (64 ± 9 years, 4 female). The functional network was constructed using 141 by 141 region-to-region functional connectivity metrics (RRC) and network-based statistic was carried out (connection threshold p < 0.001, cluster threshold pFDR < 0.05). RESULTS: In total, 9870 functional connections were analyzed. PSPs compared to aged non-AD MCI reference group expressed aberrant connectivity evidenced by the significant NBS network consisting of 89 ROIs and 118 connections among them (NBS mass 4226, pFDR < 0.05). Tau load in the right globus pallidus externus (GPe) and left dentate nucleus (DN) showed significant effects on functional network connectivity. The network linked with increased tau load in the right GPe was associated with hyperconnectivity of low-range intra-opercular connections (NBS mass 356, pFDR < 0.05), while the network linked with increased tau load in the left cerebellar DN was associated with cerebellar hyperconnectivity and cortico-cerebellar hypoconnectivity (NBS mass 517, pFDR < 0.05). CONCLUSIONS: PSP patients show altered functional connectivity. Network incorporating deep gray matter structures demonstrate hypoconnectivity, cerebellum hyperconnectivity, while cortico-cortical connections show variable changes. Tau load in the right GPe and left DN is associated with functional networks which strengthen low-scale intra-opercular and intra-cerebellar connections and weaken opercular-cerebellar connections. These findings support the concept of tau load-dependent functional network changes in PSP, by that providing evidence for downstream effects of neuropathology on brain functionality in this primary tauopathy.

Predicting intracerebral hemorrhage by baseline magnetic resonance imaging in stroke patients undergoing systemic thrombolysis.

OBJECTIVES: Intracerebral hemorrhage (ICH) remains a serious complication in ischemic stroke patients undergoing systemic thrombolysis. Here, we examined whether the risk of treatment-associated hemorrhage can be predicted from magnetic resonance imaging (MRI) using fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) within 3 h after symptom onset. METHODS: In this single-center observational study involving 122 ischemic stroke patients between January 2005 and December 2008, the incidence of FLAIR-positive lesions within diffusion-restricted areas was determined on baseline MRI, which was carried out prior to treatment with tissue plasminogen activator (Actilyse(®) ) within 3 h from symptom onset. The rate of ICH was assessed by computed tomography performed within 24 h after treatment. Relationships between FLAIR-positive lesions, DWI lesion size, proportion of FLAIR/DWI-positive lesions, and occurrence of bleeding were explored. RESULTS: Data from 97 patients were evaluated. FLAIR-positive lesions were present in 25 patients (25.8%) and ICH occurred in 32 patients (33.0%). FLAIR-positive lesions were associated with a bleeding rate of 80.0% compared with 16.7% in FLAIR-negative patients (P < 0.001; odds ratio 20.0, positive predictive value 0.8). DWI lesion size was significantly correlated with the rate of ICH (P = 0.001). In contrast, FLAIR/DWI proportion was not associated with ICH (P = 0.788). CONCLUSIONS: In ischemic stroke patients within 3 h from symptom onset, the existence of FLAIR-positive lesions on pretreatment MRI is significantly associated with an increased bleeding risk due to systemic thrombolysis. Therefore, considering FLAIR-positive lesions on baseline MRI might guide treatment decisions in ischemic stroke.

[Deep brain stimulation using simultaneous stereotactic electrode placement: an alternative to conventional functional stereotaxy?]. / Tiefe Hirnstimulation mittels simultaner stereotaktischer Elektrodenplatzierung : Eine Alternative zur konventionellen funktionellen Stereotaxie?

BACKGROUND: Deep brain stimulation (DBS) has become a reliable method in the treatment of movement disorders, e.g. idiopathic Parkinson's disease (IPD) and is technically based on stereotaxy. The Starfix® platform is a new type of stereotactic frame that allows an individualized and patient-optimized therapeutic regimen in IPD. OBJECTIVES: The aim of this study was to retrospectively compare the outcomes of IPD patients who underwent surgery with the use of conventional stereotactic frames (31 patients) to those who underwent implantation of DBS with the use of Starfix® frames (29 patients). MATERIAL AND METHODS: Surgery time, the unified Parkinson's disease rating scale III (UPDRS/III) score, L-dopa and L-dopa equivalent doses (LED) were compared prior to surgery as well as 4 weeks, 12 weeks, 6 months and 1 year postoperatively. RESULTS: The IPD-related symptoms improved significantly in both groups with respect to the UPDRS III score (conventional 69.6% vs. 72.4% Starfix®). After surgery significant reductions of L-dopa and LED were seen in both groups. Inherent advantages of the Starfix® platform included simultaneous positioning of the stimulating electrodes and a significant reduction in surgical time. CONCLUSION: In summary, both stereotactic procedures are reliable and safe procedures for the placement of stimulating electrodes as well as the stimulation effect achieved. The logistical uncoupling of presurgical planning from surgical therapy emphasizes the benefits of the individualized stereotactic procedure.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer.

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

[Critical illness myopathy and neuropathy (CRIMYN). Electroneurographic classification]. / Critical-illness-Myopathie und -Neuropathie (CRIMYN). Elektroneurographische Klassifikation.

BACKGROUND: Critical Illness Myopathy and Neuropathy (CRIMYN) frequently coexist with severe sepsis and is associated with prolonged weaning from mechanical ventilation and prolonged ICU length of stay. We aimed to classify different levels as well as patterns of impairment with regard to electrophysiological disturbances in CRIMYN patients by cluster analysis. METHODS: A total of 30 patients with sepsis/SIRS were studied prospectively. Motor and sensory conduction studies were performed from six motor and four sensory nerves on a weekly basis from admission until discharge and finally after 6 months. A control group of 63 healthy persons was examined simultaneously using the same criteria. Different patterns of electrophysiological disturbances were classified by cluster analysis based on differences to reference values of 20 parameters, compound muscle action potential (CMAP), sensory nerve action potential (SNAP) and motor and sensor conduction velocity (NCV). RESULTS: Four different clusters were identified: cluster 1 showing normal values for CMAP, SNAP and NCV in all nerves (3 patients and all test persons), cluster 2 showing pathological values for CMAP in the lower extremities and the other parameters were normal (5 patients), cluster 3 showing moderately pathological values for CMAP, SNAP and sensory NCV in upper and lower extremities and motor NCV in lower extremities (12 patients) and cluster 4 showing severe disturbances of CMAP, SNAP and NCV in upper and lower extremities (10 patients). CONCLUSION: A total of four different clusters of electrophysiological impairment can be identified in patients with sepsis/SIRS, which enables further differentiation of the severity of neuromuscular disturbances in sepsis-associated organ failure. This might be useful as a prognostic parameter and can be correlated with additional clinical and paraclinical parameters related to sepsis.

[Early symptoms and findings in optic nerve meningiomas]. / Erstsymptome und Befunde bei Meningeomen des N. opticus.

PURPOSE OF THE STUDY: While evaluating radiotherapy results in patients with primary and secondary optic nerve sheath meningiomas (ONSM) treated between 1993 and 2002, a large amount of data about early signs and symptoms has been collected which might be helpful for establishing an early diagnosis. METHODS: We have reviewed the charts of the patients available at the Centre of Ophthalmology, collecting especially pretreatment data. RESULTS: 112 patients, 4 with bilateral tumours, 83 % female were included. Mean age was 51.7 years. Visual acuity loss with relative afferent pupillary defect was the main symptom and sign in primary ONSM (38 patients). Median interval between first symptoms and diagnosis was 12 months. Optic discs were in approximately one half atrophic, the other half were swollen, and only rarely normal (3 cases only). Retinociliary shunt vessels were seen in 10 cases. Nerve fibre bundle defects were the major visual field finding (including constriction and central scotoma). Visual acuity was better than 0.5 (20 / 40) in 46 % and worse than 0.1 (20 / 200) in 30 %. In secondary ONSM, the interval to diagnosis was with a median of 6 months shorter than in primary ONSM. Approximately half of the optic discs were atrophic, only 6 % were swollen. Even here nerve fibre bundle defects were dominating, only 7 % had vertical hemianopic defect. Visual acuity was better than 0.5 (20 / 40) in 30 % and in worse than 0.1 (20 / 200) 22 %. 45 % had ocular motility disorders. DISCUSSION: Vertical hemianopic defects were surprisingly rare. The high rate of nerve fibre bundle defects and the relatively high number of patients with good visual acuity might explain why this disorder is occasionally mistaken for glaucoma. A typical clinical appearance can be outlined: mainly mid-aged women, slowly progressing visual loss, frequently motility disorders, relative afferent pupillary defect, nerve fibre bundle defects and atrophic or--mainly in primary ONSM--swollen optic disc form the characteristic picture.

[Plasticity of the motor system in multiple sclerosis]. / Plastizität des motorischen Systems bei Multipler Sklerose.

Multiple Sclerosis (MS) is associated with a chronic demyelinating and axonal injury to the central nervous system. Functional activation studies in MS patients have demonstrated that performance of simple motor tasks may activate non-canonical brain regions. Using virtual lesion induction by transcranial magnetic stimulation, it is possible to show that this activation is functionally relevant. Rapid-onset neuronal plasticity in patients with mild-to-moderate MS is uncompromised despite many plasticity-impeding factors. Long-term adaptive mechanisms, relying on the formation on new neuronal connections, most likely are the principal mechanism underlying compensation of brain injury in MS.

Testing for food-specific antibodies in saliva and blood of food allergic and healthy dogs.

An elimination diet (ED) followed by re-challenge has been the reference standard to diagnose adverse food reactions (AFR) in dogs, but can be challenging to conduct. This study investigated the accuracy of a saliva-based test for food-specific IgA and IgM and an ELISA serum test for food-specific IgE. Three groups of dogs were tested. Group 1 (n=11) included dogs with previously diagnosed and controlled AFR; group 2 (n=15) comprised dogs with allergic dermatitis at the beginning of their ED; and group 3 (n=16) was composed of clinically healthy research dogs. Saliva samples were collected from all groups and blood samples from group 1 and group 3. The results of clinical re-challenges with individual food components were compared with the test results. Specificity, sensitivity, positive and negative predictive values and likelihood ratios were determined. Forty-one dogs completed the study; one dog was lost to follow up. There was a total of 163 re-challenges. Sensitivity, positive predictive value and likelihood ratio, specificity, negative predictive value and likelihood ratios were unsatisfactory for both tests in most instances, except for IgM testing in group 2, which had moderate specificity. There was no clear difference in the number of positive reactions between the allergic dogs and healthy dogs from a research population. Based on these results, the saliva test for food specific IgA and IgM and the ELISA serum test for food specific IgE were not reliable to diagnose adverse food reactions in dogs. Until more data are available, elimination diets remain the reference standard in the diagnosis of this disease.

Tallness is associated with risk of testicular cancer: evidence for the nutrition hypothesis.

The pathogenesis of testicular germ cell tumours (GCTs) is potentially influenced by high-energy nutrition during infancy. As adult height is a proxy for childhood nutrition, we investigated the role of nutrition in GCT pathogenesis by comparing stature of patients with healthy men. In a matched case-control study, 6415 patients with GCT were compared with healthy army conscripts (1:6 matching modus) with regard to height (cm) and body mass index (BMI; kg/m(2)). Statistical analysis involved tabulation of descriptive height measures and BMI. Conditional logistic regression models were used to quantify the association of GCT with height, with odds ratios (OR) adjusted for BMI. The literature was searched for studies on stature in GCT patients. Body size is significantly associated with risk of GCT, very tall men (>195 cm) having a GCT risk of OR=3.35 (95% confidence intervals (CI): 2.88-3.90; adjusted). Short stature is protective (OR=0.798; 95% CI: 0.68-0.93). Both histologic subgroups are associated with tallness. Of 16 previous reports, 7 were confirmative, 5 had null and 4 equivocal results. The association of stature with GCT risk accords with the nutrition hypothesis of GCT. This study expands the current view of GCT tumorigenesis by suggesting that high-calorie intake in childhood promotes GCT precursors originating in utero.

Concurrent action observation modulates practice-induced motor memory formation.

Motor practice is associated with the formation of elementary motor memories. Here we tested in human subjects the hypothesis that observation of a motor training associated with physical practice will modulate the encoding process of a motor memory relative to physical practice alone. Voluntary thumb motions were practiced (i) alone in a direction opposite to the baseline direction of transcranial magnetic stimulation (TMS)-evoked movements (physical practice, PP) and in combination with observation of synchronous movements that were either (ii) directionally congruent (same direction, PP + AOc) or (iii) non-congruent (opposite direction, PP + AOnc) to the practiced ones. We evaluated the following measures of motor memory formation: percentage of TMS-evoked thumb movements falling in the direction of practiced motions, acceleration of TMS-evoked movements along the principal movement axis and corticomuscular excitability of training muscles as indexed by motor-evoked potential amplitudes. Both PP and PP + AOc, but not PP + AOnc, significantly increased the percentage of TMS-evoked movements falling in the practiced direction, changed the compound acceleration vector into the trained direction and enhanced the motor-evoked potential amplitudes in the training agonist muscle. The percentage of TMS-evoked movements falling in the practiced direction increased significantly more after PP + AOc than after PP. Across all measures of motor memory formation, PP + AOc was most efficacious, followed by PP and PP + AOnc. Action observation modulates practice effects on formation of a motor memory. Strengthening of the process of motor memory encoding depends on the directional congruency of the observed model.

Preliminary evaluation of cytosine-phosphate-guanine oligodeoxynucleotides bound to gelatine nanoparticles as immunotherapy for canine atopic dermatitis.

Cytosine-phosphate-guanine oligodeoxynucleotides (CpG ODN) are a promising new immunotherapeutic treatment option for canine atopic dermatitis (AD). The aim of this uncontrolled pilot study was to evaluate clinical and immunological effects of gelatine nanoparticle (GNP)-bound CpG ODN (CpG GNP) on atopic dogs. Eighteen dogs with AD were treated for 8 weeks (group 1, n=8) or 18 weeks (group 2, n=10). Before inclusion and after 2 weeks, 4 weeks, 6 weeks (group 1+2), 8 weeks, 12 weeks and 16 weeks (group 2) 75 µg CpG ODN/dog (bound to 1.5 mg GNP) were injected subcutaneously. Pruritus was evaluated daily by the owner. Lesions were evaluated and serum concentrations and mRNA expressions of interferon-γ, tumour necrosis factor-α, transforming growth factor-ß, interleukin (IL) 10 and IL-4 (only mRNA expression) were determined at inclusion and after 8 weeks (group 1+2) and 18 weeks (group 2). Lesions and pruritus improved significantly from baseline to week 8. Mean improvements from baseline to week 18 were 23 per cent and 44 per cent for lesions and pruritus, respectively, an improvement of ≥50 per cent was seen in six out of nine and three out of six dogs, respectively. IL-4 mRNA expression decreased significantly. The results of this study show a clinical improvement of canine AD with CpG GNP comparable to allergen immunotherapy. Controlled studies are needed to confirm these findings.

The associative brain at work: Evidence from paired associative stimulation studies in humans.

The original protocol of Paired Associative Stimulation (PAS) in humans implies repetitive cortical and peripheral nerve stimuli, delivered at specific inter-stimulus intervals, able to elicit non-invasively long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity in the human motor cortex. PAS has been designed to drive cortical LTP/LTD according to the Hebbian rule of associative plasticity. Over the last two decades, a growing number of researchers have increasingly used the PAS technique to assess cortical associative plasticity in healthy humans and in patients with movement disorders and other neuropsychiatric diseases. The present review covers the physiology, pharmacology, pathology and motor effects of PAS. Further sections of the review focus on new protocols of "modified PAS" and possible future application of PAS in neuromorphic circuits designed for brain-computer interface.

Comparison of ultrasound imaging and video otoscopy with cross-sectional imaging for the diagnosis of canine otitis media.

Ultrasound imaging (US) of the tympanic bulla (TB) for diagnosis of canine otitis media (OM) is less expensive and less invasive than cross-sectional imaging techniques including computed tomography (CT) and magnetic resonance imaging (MRI). Video otoscopy (VO) is used to clean inflamed ears. The objective of this study was to investigate the diagnostic value of US and VO in OM using cross-sectional imaging as the reference standard. Client owned dogs with clinical signs of OE and/or OM were recruited for the study. Physical, neurological, otoscopic and otic cytological examinations were performed on each dog and both TB were evaluated using US with an 8 MHz micro convex probe, cross-sectional imaging (CT or MRI) and VO. Of 32 dogs enrolled, 24 had chronic otitis externa (OE; five also had clinical signs of OM), four had acute OE without clinical signs of OM, and four had OM without OE. Ultrasound imaging was positive in three of 14 ears, with OM identified on cross-sectional imaging. One US was false positive. Sensitivity, specificity, positive and negative predictive values and accuracy of US were 21%, 98%, 75%, 81% and 81%, respectively. The corresponding values of VO were 91%, 98%, 91%, 98% and 97%, respectively. Video otoscopy could not identify OM in one case, while in another case, although the tympanum was ruptured, the CT was negative. Ultrasound imaging should not replace cross-sectional imaging for the diagnosis of canine OM, but can be helpful, and VO was much more reliable than US.

Enhancement of use-dependent plasticity by D-amphetamine.

In healthy individuals, motor training can elicit use-dependent plasticity. Here the authors studied six subjects in whom training alone failed to elicit this effect. Administration of a single dose of 10 mg of D-amphetamine preceding training led to use-dependent plasticity in a subgroup of these subjects. Using pharmacologic interventions to enhance the effects of motor training might help rehabilitative efforts in patients in whom training alone fails.

Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation.

We studied the effects of low-frequency transcranial magnetic stimulation (TMS) on motor cortex excitability in humans. TMS at 0.1 Hz for 1 hour did not change cortical excitability. Stimulation at 0.9 Hz for 15 minutes (810 pulses), similar to the parameters used to induce long-term depression (LTD) in cortical slice preparations and in vivo animal studies, led to a mean decrease in motor evoked potential (MEP) amplitude of 19.5%. The decrease in cortical excitability lasted for at least 15 minutes after the end of the 0.9 Hz stimulation. The mechanism underlying this decrease in excitability may be similar to LTD. TMS-induced reduction of cortical excitability has potential clinical applications in diseases such as epilepsy and myoclonus. Spread of excitation, which may be a warning sign for seizures, occurred in one subject and was not accompanied by increased MEP amplitude, suggesting that spread of excitation and amplitude changes are different phenomena and also indicating the need for adequate monitoring even with stimulations at low frequencies.

Acute abdominal complications of systemic lupus erythematosus and polyarteritis nodosa.

Fifteen (11 percent) of 140 patients with systemic lupus erythematosus (SLE) and five (31 percent) of 16 patients with polyarteritis nodosa (PA) developed disease-related signs and symptoms of an acute surgical abdomen. Peripheral vasculitis (p less than 0.025), nervous system involvement (p less than 0.05), ischemic necrosis of bone (p less than 0.05), thrombocytopenia (p less than 0.01), and circulating rheumatoid factor (p less than 0.01) are all significantly more prevalent in patients with SLE and abdominal involvement compared with those without an abdominal syndrome. Similarly, except for ischemic necrosis of bone, these same features are more prevalent in patients with PA and acute abdomens. Eleven (73 percent) of 15 patients with SLE had exploratory laparotomy for acute abdominal events. Nine were found to have evidence of intra-abdominal arteritis and only two had polyserositis without gross evidence of vasculitis. Eight (53 percent) of the 15 patients with SLE and acute abdomens died as a result of their abdominal crises. Six of the seven surviving patients represent those most recently seen and aggressively treated. All five patients with PA and acute abdomens required operative intervention and all had gross evidence of mesenteric arteritis with large ischemic segments resulting in infarction and perforation. All died in contrast to only two (18 percent) of the 11 PA patients without abdominal involvement.

Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: a prospective multicenter study.

PURPOSE: A prospective multicenter study was carried out to estimate the treatment outcome of radiotherapy in Stage II seminoma after the application of modern staging and radiotherapy techniques. The lower margin of the iliac field was positioned on the upper rim of the acetabulum to reduce the amount of scattered irradiation to the remaining testicle. METHODS AND MATERIALS: The study was carried out in 25 centers in Germany. Patients with pure seminoma, negative AFP-values, and retroperitoneal lymph node metastases of less than 5 cm in diameter were entered into the study. All patients received a ventrodorsal opposed field irradiation of the para-aortic and the ipsilateral iliac lymph nodes. The fields extended from the top of the 11th thoracic vertebra to the top of the acetabulum. Patients in Stage IIA (lymph nodes <2 cm ) received 30 Gy, and patients with Stage IIB (lymph nodes between 2 and 5 cm) 36 Gy total dose. RESULTS: 39 patients in Stage IIA and 19 patients in Stage IIB were evaluated. After a median observation time of 37 months all patients are alive and disease free. Recurrence free survival in stage IIA was 100%. Two patients in Stage IIB experienced a recurrence 10 and 17 months after the end of radiotherapy. The actuarial recurrence free survival estimate in Stage IIB was 94.1% for 1 year and 87.4% for 2 years. One recurrence in Stage IIB occurred in the mediastinum, one in the mediastinum, and one the lung. Both patients could be salvaged by chemotherapy. There were no pelvic recurrences. The treatment was well tolerated, with nausea being the most common side effect (56.9% Grade 1, 15.5% Grade 2, and 8.6% Grade 3). Diarrhea occurred in 15.5% (Grade 1), 15.5% (Grade 2), and 5.2% (Grade 3) of the patients. CONCLUSIONS: The outcome of para-aortic and ipsilateral iliac irradiation in Stage IIA/B testicular seminoma is excellent with the currently available staging methods and treatment facilities. The treatment is well tolerated. The lower margin of the iliacal field can be placed at the acetabulum.