Voluntary pelvic floor muscle control - An fMRI study

Storage and periodic expulsion of urine by the bladder are controlled by central pathways and organized as simple on-off switching circuits. Several reports concerning aspects of micturition control have identified distinct regions in the brainstem, like the pontine micturition center (PMC) and the periaqueductal gray (PAG), as well as the cerebellum, basal ganglia, limbic system, and cortical areas that are organized in a widespread network. The present study focused on the involvement of these specific brain regions in pelvic floor muscle control. Functional magnetic resonance imaging (fMRI) was performed at 3T in 11 healthy women with urge to void due to a filled bladder, who were instructed to either imitate voiding by releasing or to imitate interruption of voiding by contracting pelvic floor muscles. None of the subjects was able to start voiding during the experiments, presumably due to subconscious restraint resulting from the inconvenient situation. Relaxation and contraction of pelvic floor muscles induced strong and similar activation patterns including frontal cortex, sensory-motor cortex, cerebellum, and basal ganglia. Furthermore, well-localized activations in the PMC and the PAG were identified. To our knowledge, this is the first study using fMRI to demonstrate micturition-related activity in these brainstem structures. The presented approach proved to characterize the widespread central network in pelvic floor muscle control. Thus, in patients with voiding dysfunction, fMRI will be useful to elucidate the individual disturbance level. (c) 2006 Elsevier Inc. All rights reserved

Risk factors for perioperative complications in renal surgery for Wilms' tumor

Background: There is controversy about preoperative chemotherapy in the treatment of Wilms' tumor. The perioperative morbidity plays a key role in this discussion. Therefore, risk factors of perioperative complications were analysed in our series of patients with Wilms' tumor with a special focus on the effects of preoperative chemotherapy. Patients and Methods: Case histories of 37 patients [mean age 3.9 (range: 0.6 - 14) years I were retrospectively analysed concerning follow-up, clinical and histopathological stage, size of the primary tumor, as well as duration and extent of preoperative chemotherapy. Results: 35 patients underwent radical nephrectomy, 2 patients had organ-sparing surgery because of bilateral involvement. The mean maximal tumor diameter was 9.5 cm (range: 4-24cm). 11/37 patients had no or shortened preoperative chemotherapy. 6/37 patients (16.2%) had perioperative complications. There was one intraoperative tumor rupture, 4 small bowel obstructions, I pancreatitis. All complications occurred in patients of clinical stages III and IV, maximal tumor diameter > 10 cm after unusually extended operative procedures. 4 patients showed only poor response to preoperative chemotherapy. Patients with doxorubicin pretreatment showed a higher risk of postoperative small bowel obstruction. Conclusions: The risk of perioperative complications was correlated with the local extent of the primary tumor and was higher with those requiring more extensive surgical interventions. The influence of preoperative chemotherapy on the complications rate is inconstant. Considering a good response of the primary tumor, the complication rate will be decreased. However, the comorbidity of more intense preoperative chemotherapy in patients of stage IV may contribute to a higher risk of surgical complications

Long-term clinical outcome in patients with stage-i nonseminomatous germ cell cancer: a critical review of own treatment modalities in a retrospective study

PURPOSE: The optimal management of patients with clinical stage I non-seminomatous germ cell testicular cancer (NSGCT I) was considered controversial until the European Germ Cell Cancer Consensus Group determined unambiguous treatment strategies. In order to assess the long-term outcome we evaluated the data of patients with NSGCT I. MATERIALS AND METHODS: In a retrospective evaluation, we included 52 patients with a mean age of 26 years (range 15-58) who were treated with different modalities at our department between 1989 and 2003. Mean follow-up was 5.9 years (range 2-14 years). After orchiectomy, 39 patients were treated with chemotherapy, 7 patients underwent retroperitoneal lymph node dissection and 6 men were managed using a surveillance strategy. Survival, recurrence rate and time of recurrence were evaluated. The histological staging and treatment modality was related to the relapse. RESULTS: Tumor specific overall mortality was 3.8%. The mortality and relapse rate of the surveillance strategy, retroperitoneal lymph node dissection and chemotherapy was 16.7% / 50%, 14.3% / 14.3% and 0% / 2.5% respectively. All relapsed patients in the surveillance group as well as in the RPLND group had at least one risk factor for developing metastatic disease. CONCLUSIONS: Following the European consensus on diagnosis and treatment of germ cell cancer in patients with NSGCT Stage I any treatment decision must be individually related to the patient according to prognostic factors and care capacity of the treating centre. In case of doubt, adjuvant chemotherapy should be the treatment of choice, as it provides the lowest risk of relapse or tumor related death

Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Prostate Cancer: The Primary Results of the PRONOUNCE Randomized Trial

BackgroundThe relative cardiovascular safety of gonadotropin-releasing hormone (GnRH) antagonists compared with GnRH agonists in men with prostate cancer and known atherosclerotic cardiovascular disease remains controversial.MethodsIn this international, multicenter, prospective, randomized, open-label trial, men with prostate cancer and concomitant atherosclerotic cardiovascular disease were randomly assigned 1:1 to receive the GnRH antagonist degarelix or the GnRH agonist leuprolide for 12 months. The primary outcome was the time to first adjudicated major adverse cardiovascular event (composite of death, myocardial infarction, or stroke) through 12 months.ResultsBecause of slower-than-projected enrollment and fewer-than-projected primary outcome events, enrollment was stopped before the 900 planned participants were accrued. From May 3, 2016, to April 16, 2020, a total of 545 patients from 113 sites across 12 countries were randomly selected. Baseline characteristics were balanced between study groups. The median age was 73 years, 49.8% had localized prostate cancer; 26.3% had locally advanced disease, and 20.4% had metastatic disease. A major adverse cardiovascular event occurred in 15 (5.5%) patients assigned to degarelix and 11 (4.1%) patients assigned to leuprolide (hazard ratio, 1.28 [95% CI, 0.59-2.79]; P=0.53).ConclusionsPRONOUNCE (A Trial Comparing Cardiovascular Safety of Degarelix Versus Leuprolide in Patients With Advanced Prostate Cancer and Cardiovascular Disease) is the first, international, randomized clinical trial to prospectively compare the cardiovascular safety of a GnRH antagonist and a GnRH agonist in patients with prostate cancer. The study was terminated prematurely because of the smaller than planned number of participants and events, and no difference in major adverse cardiovascular events at 1 year between patients assigned to degarelix or leuprolide was observed. The relative cardiovascular safety of GnRH antagonists and agonists remains unresolved. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02663908