Identification of brain structures involved in micturition with functional magnetic resonance imaging (fMRI)

OBJECTIVE: The voluntary control of micturition is believed to be integrated by complex interactions among the brainstem, subcortical areas and cortical areas. Several brain imaging studies using positron emission tomography (PET) have demonstrated that frontal brain areas, the limbic system, the pons and the premotor cortical areas were involved. However, the cortical and subcortical brain areas have not yet been precisely identified and their exact function is not yet completely understood. MATERIALS AND METHODS: This study used functional magnetic resonance imaging (fMRI) to compare brain activity during passive filling and emptying of the bladder. A cathetherism of the bladder was performed in seven healthy subjects (one man and six right-handed women). During scanning, the bladder was alternatively filled and emptied at a constant rate with bladder rincing solution. RESULTS: Comparison between passive filling of the bladder and emptying of the bladder showed an increased brain activity in the right inferior frontal gyrus, cerebellum, symmetrically in the operculum and mesial frontal. Subcortical areas were not evaluated. CONCLUSIONS: Our results suggest that several cortical brain areas are involved in the regulation of micturition.

Sexual and organ function in patients with symptomatic prolapse: are pessaries helpful?

OBJECTIVE: To evaluate quality of life and pelvic organ and sexual function before and during pessary use in patients with symptomatic pelvic organ prolapse and to determine reasons which lead to cessation of pessary use. DESIGN: Prospective observational study. SETTING: Tertiary referral center. PATIENT(S): Patients with symptomatic stage II or more prolapse of the anterior, posterior, or apical vaginal wall with or without uterus were included in this study. INTERVENTION(S): We used the Female Sexual Function Index questionnaire and the Sheffield prolapse questionnaire. For quality of life we used the King's Health Questionnaire. MAIN OUTCOME MEASURE(S): Main outcome measures were quality of life and sexual and pelvic organ function. RESULT(S): A total of 73 women participated in this study; 31 were sexually active. Desire, lubrication, and sexual satisfaction showed statistically significant improvement, and orgasm remained unchanged. Statistically significant improvement in the feeling of bulge occurred during therapy, stool outlet problems were significantly improved, overactive bladder symptoms were significantly better, and pessaries did not significantly alter incontinence. CONCLUSION(S): Pessaries have been shown to be a viable noninvasive treatment for pelvic organ prolapse improving organ and sexual function as well as general wellbeing.

Sexual function after suburethral sling removal for dyspareunia

INTRODUCTION: Impact on sexual function has received little attention in the medical literature for a long time. Because of the site of insertion of permanent tension free vaginal tape (TVT) the G spot might be affected or the tape might interfere with arousal and sensory stimulation. Recent studies have reported varying degrees of sexual impairment after TVT insertion ranging from 0% to 15% including dyspareunia. AIM: The aim of this study was to evaluate sexual function before and after suburethral sling removal due to postoperative female de novo dyspareunia. As a secondary outcome, general patients' satisfaction with their overall continence situation was assessed. PATIENTS AND METHODS: Between December 2005 and December 2007, we included 18 female patients who complained of de novo dyspareunia after suburethral sling insertion for urinary stress incontinence. All patients filled in an FSFI questionnaire prior to sling removal and at 3 months postoperatively. Additionally, all women were asked to estimate their general satisfaction regarding their continence situation using a Visual Analogue Scale (VAS) from 0 to 10, with 0 being the least satisfying situation and 10 being the most satisfying situation. All patients underwent gynaecological examination including ICS-pelvic organ prolapse staging (ICS-POP score). RESULTS: Of the 18 slings, ten were transobturator tapes (6 x TVT-O, 2 x Monarch, 2 x unknown) and eight were retropubic tapes (7 x TVT, 1 x SPARC). Desire, arousal, lubrication, satisfaction, and pain improved statistically significant. Orgasm scores were low with median scoring of 1.5 scores before and 1.0 scores after sling removal, and they did not change significantly after sling removal. The satisfaction rate deteriorated from a median of 7 (95% confidence interval [CI] 6.3-7.7) to a median of 4 (95% CI 3.7-5.1; p=0.99) but not statistically significant. CONCLUSIONS: Sexual function in patients with de novo dyspareunia is likely to improve after sling removal but not in all domains. Bladder function may deteriorate.

Outcome after radical cystectomy with limited or extended pelvic lymph node dissection

PURPOSE: We compared recurrence patterns and survival of patients with urothelial bladder cancer undergoing radical cystectomy who either had limited or extended pelvic lymph node dissection at 2 institutions between 1987 and 2000. MATERIALS AND METHODS: Two consecutive series of patients treated with radical cystectomy and limited pelvic lymph node dissection (336; Cleveland Clinic) and extended pelvic lymph node dissection (322; University of Bern) were analyzed. All cases were staged N0M0 prior to radical cystectomy, and none were treated with neoadjuvant radiotherapy or chemotherapy. Patients with PTis/pT1 and pT4 disease were excluded from analysis. Pathological characteristics based on the 1997 TNM system and recurrence patterns were determined. RESULTS: The overall lymph node positive rate was 13% for patients with limited and 26% for those who had extended pelvic lymph node dissection. The 5-year recurrence-free survival of patients with lymph node positive disease was 7% for limited and 35% for extended pelvic lymph node dissection. The 5-year recurrence-free survival for pT2pN0 cases was 67% for limited and 77% for extended pelvic lymph node dissection, and the respective percentages for pT3pN0 cases were 23% and 57% (p <0.0001). The 5-year recurrence-free survival for pT2pN0-2 cases was 63% for limited and 71% for extended pelvic lymph node dissection, and for pT3pN0-2 cases the respective figures were 19% and 49% (p <0.0001). Incidence of local and systemic failure correlated closely with pathological stage for both series. CONCLUSIONS: Our data suggest that limited pelvic lymph node dissection is associated with suboptimal staging, poorer outcome for patients with node positive and node negative disease, and a higher rate of local progression. Extended pelvic lymph node dissection allows for more accurate staging and improved survival of patients with nonorgan confined and lymph node positive disease.

A safe and simple solution for intravesical tension-free vaginal tape erosion: removal by standard transurethral resection

OBJECTIVE: To report our experience with the successful removal of visible tension-free vaginal tape (TVT) by standard transurethral electroresection, as intravesical tape erosion after TVT is a rare complication, and removal can be challenging, with few cases reported. PATIENTS AND METHODS: Five patients presenting with TVT erosion into the bladder were treated at our institutions from December 2004 to July 2007; all had standard transurethral electroresection. Their records were reviewed retrospectively to retrieve data on presenting symptoms, diagnostic tests, surgical procedures and outcomes. RESULTS: The median (range) interval between the TVT procedure and the onset of symptoms was 17 (1-32) months. The predominant symptoms were painful micturition, recurrent urinary tract infection (UTI), urgency and urge incontinence. There were no complications during surgery. The storage symptoms and UTI resolved completely after removing the eroded mesh in all but one patient. Cystoscopy at 1 month after surgery showed complete healing of the bladder mucosa. CONCLUSION: Although TVT erosion into the bladder is rare, persistent symptoms, particularly recurrent UTIs, must raise some suspicion for this condition. Standard transurethral electroresection seems to be a safe, simple, minimally invasive and successful treatment option for TVT removal.

Low-grade endometrial stromal sarcoma with inferior vena cava tumor thrombus and intracardiac extension: radical resection may improve recurrence free survival

BACKGROUND: Endometrial stromal sarcoma (ESS) represents 0.2% of all uterine malignancies. Based on the mitotic activity, a distinction is made between low and high-grade ESS. Although the overall five-year survival rate for low-grade ESS exceeds 80%, about 50% of the patients show tumor recurrence, mostly after a long latency period. Tumor invasion of the great vessels is extremely rare. We describe a patient with advanced low-grade ESS with tumor invasion of the infrarenal aorta and the inferior vena cava. The patient presented with a large tumor thrombus extending from the inferior vena cava into the right atrium. METHODS: Review of literature and identification of 19 patients, including our own case report, with advanced low-grade ESS with invasion of the great vessels and formation of an inferior vena cava tumor thrombus. RESULTS: All 19 patients presented with an abdominal tumor mass and a tumor thrombus protruding into the inferior vena cava. The tumor thrombus extended into the right heart cavities in nine patients reaching the right atrium in four, the right ventricle in three and the pulmonary artery in two patients. There were 5 patients with an advanced primary tumor and 14 patients with an advanced recurrent tumor. Seven patients presented with synchronous metastatic disease and six patients with a pelvic tumor infiltrating the bladder, the rectosigmoid colon or the infrarenal aorta. Mean age at surgery was 45.9+/-12.3 years (median 47, range 25-65 years). Tumor thrombectomy was accomplished by cavatomy or by right atriotomy after installation of a cardiopulmonary bypass. There was no peri-operative mortality and a very low morbidity. Radical tumor resections were achieved in 10 patients. The follow-up for these 10 patients was 2+/-1.3 years (median 2, range 0.3-4.5 years). Nine patients remained recurrence free whereas one patient suffered an asymptomatic local recurrence. CONCLUSIONS: Low-grade ESS is a rare angioinvasive tumor with a high recurrence rate. Resection of an inferior vena cava tumor thrombus, even with extension into the right heart cavities, can be performed safely. Extensive radical surgery is therefore justified in the treatment of advanced tumor manifestations of a low-grade ESS potentially improving recurrence free survival.

Long-term outcome of acute spinal cord ischemia syndrome

BACKGROUND AND PURPOSE: Current knowledge of long-term outcome in patients with acute spinal cord ischemia syndrome (ASCIS) is based on few studies with small sample sizes and <2 years' follow-up. Therefore, we analyzed clinical features and outcome of all types of ASCIS to define predictors of recovery. METHODS: From January 1990 through October 2002, 57 patients with ASCIS were admitted to our center. Follow-up data were available for 54. Neurological syndrome and initial degree of impairment were defined according to American Spinal Injury Association (ASIA)/International Medical Society of Paraplegia criteria. Functional outcome was assessed by walking ability and bladder control. RESULTS: Mean age was 59.4 years; 29 were women; and mean follow-up was 4.5 years. The origin was atherosclerosis in 33.3%, aortic pathology in 15.8%, degenerative spine disease in 15.8%, cardiac embolism in 3.5%, systemic hypotension in 1.8%, epidural anesthesia in 1.8%, and cryptogenic in 28%. The initial motor deficit was severe in 30% (ASIA grades A and B), moderate in 28% (ASIA C), and mild in 42% (ASIA D). At follow-up, 41% had regained full walking ability, 30% were able to walk with aids, 20% were wheelchair bound, and 9% had died. Severe initial impairment (ASIA A and B) and female sex were independent predictors of unfavorable outcome (P=0.012 and P=0.043). CONCLUSIONS: Considering a broad spectrum of clinical presentations and origins, the outcome in our study was more favorable than in previous studies reporting on ASCIS subgroups with more severe initial deficits.

The pharmacokinetic profile of fesoterodine: similarities and differences to tolterodine

BACKGROUND: Fesoterodine is a new antimuscarinic agent developed for the treatment of overactive bladder. Fesoterodine itself is inactive and is rapidly and extensively converted by ubiquitous esterases to its principal active moiety, 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is formed via biotransformation of both fesoterodine and tolterodine, albeit by different metabolising enzymes, viz. esterases and CYP2D6 respectively. Tolterodine is a potent muscarinic receptor antagonist and has been used for the treatment of overactive bladder for over ten years. The objective of this study was to establish the pharmacokinetic profile of fesoterodine and to highlight ist potential pharmacokinetic advantages over tolterodine. DESIGN: Single-centre, open-label, randomised, 4-way crossover study in a total of 24 healthy male volunteers. Single oral doses of 4, 8, or 12 mg fesoterodine were administered after an overnight fast. In addition, the 8 mg dose was also administered after a standard high-fat and high-calorie breakfast. Blood and urine samples for the analysis of 5-HMT were collected before and multiple times after drug administration for pharmacokinetic analysis. RESULTS: The mean peak plasma concentration (Cmax) of 5-HMT and the mean area under the time versus concentration curve (AUC) increased proportionally with the fesoterodine dose. These two parameters were some 2-fold higher in CYP2D6 poor metabolisers, whereas the time to peak plasma concentration (tmax) and half life (t1/2) were not influenced by the dose or the CYP2D6 metaboliser status. If fesoterodine was taken following a high-fat breakfast, we observed small increases in Cmax and AUC. In spite of these modest genetic influences and food effects on the pharmacokinetics of fesoterodine, the overall interindividual variability in Cmax levels was relatively little compared to previously published reports using tolterodine. CONCLUSIONS: Due to the esterase-mediated cytochrome P450-independent formation of 5-HMT and involvement of multiple metabolic and renal excretion pathways in the elimination of 5-HMT, the effects of patient-intrinsic and -extrinsic factors on the pharmacokinetics of fesoterodine are only modest, with some 2-fold higher 5-HMT exposure. Therefore, in contrast to tolterodine, no reduction of fesoterodine dosage is required under conditions of reduced elimination. In most cases of drug interaction or renal/hepatic impairment, the fesoterodine dose may be increased to 8 mg/day based on individual patients' response, or patients may be required to remain at the initial recommended dose of 4 mg/day.

The murine Fgfrl1 receptor is essential for the development of the metanephric kidney

Fgfrl1 is a novel member of the fibroblast growth factor receptor family. Its extracellular domain resembles the four conventional Fgfrs, while its intracellular domain lacks the tyrosine kinase domain necessary for Fgf mediated signal transduction. During embryonic development Fgfrl1 is expressed in the musculoskeletal system, in the lung, the pancreas and the metanephric kidney. Targeted disruption of the Fgfrl1 gene leads to the perinatal death of the mice due to a hypoplastic diaphragm, which is unable to inflate the lungs. Here we show that Fgfrl1-/- embryos also fail to develop the metanephric kidney. While the rest of the urogenital system, including bladder, ureter and sexual organs, develops normally, a dramatic reduction of ureteric branching morphogenesis and a lack of mesenchymal-to-epithelial transition in the nephrogenic mesenchyme result in severe renal dysgenesis. The failure of nephron induction might be explained by the absence of the tubulogenic markers Wnt4, Fgf8, Pax8 and Lim1 at E12.5 of the mutant animals. We also observed a loss of Pax2 positive nephron precursor cells and an increase of apoptosis in the cortical zone of the remnant kidney. Fgfrl1 is therefore essential for mesenchymal differentiation in the early steps of nephrogenesis.

Detection of urinary stones at reduced radiation exposure: a phantom study comparing computed radiography and a low-dose digital radiography linear slit scanning system

OBJECTIVE: In this experimental study we assessed the diagnostic performance of digital linear slit scanning radiography compared with computed radiography (CR) for the detection of urinary calculi in an anthropomorphic phantom imitating patients weighing approximately 58-88 kg. CONCLUSION: Compared with CR, linear slit scanning radiography is superior for the detection of urinary stones and may be used for pretreatment localization and follow-up at a lower patient exposure.

Benign prostatic obstruction and parkinson's disease--should transurethral resection of the prostate be avoided?

PURPOSE: According to the literature transurethral resection of the prostate in patients with Parkinson's disease has an increased risk of postoperative urinary incontinence. However, this conclusion might have been reached because some patients with multiple system atrophy incorrectly diagnosed as Parkinson's disease were included in these reports. Therefore, we investigated the outcome of transurethral prostate resection in patients with a secure neurological diagnosis of Parkinson's disease. MATERIALS AND METHODS: A total of 23 patients with Parkinson's disease who underwent transurethral prostate resection for benign prostatic obstruction were evaluated retrospectively. Subsequent neurological developments in patients were followed, ensuring that those with multiple system atrophy had not been included in analysis. RESULTS: At transurethral prostate resection median patient age was 73 years, median duration of Parkinson's disease before the resection was 3 years, and median Hoehn and Yahr scale was 2. Of the 14 patients with a preoperative indwelling urinary catheter transurethral prostate resection restored voiding in 9 (64%) and only 5 (36%) required catheterization postoperatively. Of the 10 patients with preoperative urge urinary incontinence, continence was restored in 5 and improved in 3 following transurethral prostate resection. There were no cases of de novo urinary incontinence after transurethral prostate resection. At a median postoperative followup of 3 years transurethral prostate resection was successful in 16 of the 23 patients (70%). CONCLUSIONS: Transurethral prostate resection for benign prostatic obstruction in patients with Parkinson's disease may be successful in up to 70% and the risk of de novo urinary incontinence seems minimal. Thus, Parkinson's disease should no longer be considered a contraindication for transurethral prostate resection provided that preoperative investigations including urodynamic assessment indicate prostatic bladder outlet obstruction.

Diagnostic approach to hypercalcemia: relevance of parathyroid hormone and parathyroid hormone-related protein measurements

Background: Parathyroid hormone (PTH) and parathyroid hormone-related protein (PTH-rP) are two potent hypercalcemic hormones that act on the same targets. Autonomous secretion of the former is involved in primary hyperparathyroidism (PHPT), whereas the latter is responsible for humoral hypercalcemia of malignancy (HHM). Methods: From 250 consecutive, hypercalcemic serum samples sent to our laboratory for assessment of intact PTH, we were able to obtain clinical information, as well as an additional plasma sample for PTH-rP measurement, in 134 patients. At the time of sampling, patients could be classified into seven groups: cancer without known bone metastases (CaNoMeta, n=36), cancer with bone metastases (CaMeta, n=9), no evidence of cancer (noEvCa, n=71), sarcoidosis (Sarc, n=3), end-stage renal disease (ESRD, n=12), vitamin D overdose (VIT-D, n=2), and hyperthyroidism (Thyr, n=1). Results: In the CaNoMeta group, 29/36 patients had elevated PTH-rP levels, 9/36 patients had inappropriately elevated PTH levels, and 5/36 had elevated levels of both hormones. In the CaMeta group, three of the nine patients had inappropriately elevated PTH levels, two of them with concomitantly elevated PTH-rP levels. In the NoEvCa group, 63/71 patients had an inappropriate elevation of PTH levels and were diagnosed as having PHPT. Four of the 71 patients had elevated levels of both PTH and PTH-rP; three of them were in poor health and died within a short period of time. All of the ESRD patients had very high PTH and normal PTH-rP levels, except for one woman with high PTH-rP and undetectable PTH levels; she died from what later turned out to be a recurrent bladder carcinoma. In the Sarc, Vit-D, and Thyr groups, both PTH and PTH-rP levels were normal. Conclusions: (1) Elevated PTH-rP levels are a common finding in cancer patients without bone metastases. Intact PTH, however, should always be measured in hypercalcemic patients with malignancy because concurrent primary hyperparathyroidism is not rare. (2) Primary hyperparathyroidism accounts for hypercalcemia in 90% of patients without evidence of cancer whose PTH-rP levels may also be found to be elevated in a few cases, even some with surgically demonstrated parathyroid adenoma.

Use of EORTC Target Definition Guidelines for Dose-Intensified Salvage Radiation Therapy for Recurrent Prostate Cancer: Results of the Quality Assurance Program of the Randomized Trial SAKK 09/10

PURPOSE Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice. METHODS AND MATERIALS A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared. RESULTS Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different. CONCLUSIONS The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.

One-stage laparoscopic surgery for inspissated bile syndrome: case report and review of surgical techniques

Inspissated bile syndrome in a 6 week old boy was unresponsive to oral ursodesoxycholic acid. Intraoperative cholangiography revealed complete obstruction of the common bile duct. Therefore, the gallbladder fundus was pulled out through a laparoscopy port site and sutured to the fascia. A catheter was positioned into the infundibulum for irrigation with ursodesoxycholic acid. At day 8 complete resolution of the plug and free passage of contrast medium into the duodenum was documented radiologically. The catheter was removed, skin closed spontaneously without a second surgery for closure of the gall bladder.