Arndt van Ophoven

Clinical management of foreign bodies of the genitourinary tract.

Purpose: The variety of foreign bodies inserted into or externally attached to the genitourinary tract defies imagination and includes all types of objects. The frequency of such cases renders these objects an important addition to the diseases of the urinary organs.Materials and Methods: We performed a computerized MEDLINE search followed by a manual bibliographic review of cross-references. These reports were analyzed and the important findings summarized.Results: Our review encompassed approximately 800 single case reports on foreign bodies in the English world literature published between 1755 and 1999. We structured the range of introduced objects, by referring to origin and material as well as the genitourinary organs involved. Furthermore, we noted symptomatology and diagnoses, including psychological involvement, as well as possible treatment options.Conclusions: The most common motive associated with foreign bodies of the genitourinary tract is sexual or erotic in nature. The most suitable method...

The 2013 EAU Guidelines on Chronic Pelvic Pain: Is Management of Chronic Pelvic Pain a Habit, a Philosophy, or a Science? 10 Years of Development

CONTEXT Progress in the science of pain has led pain specialists to move away from an organ-centred understanding of pain located in the pelvis to an understanding based on the mechanism of pain and integrating, as far as possible, psychological, social, and sexual dimensions of the problem. This change is reflected in all areas, from taxonomy through treatment. However, deciding what is adequate investigation to rule out treatable disease before moving to this way of engaging with the patient experiencing pain is a complex process, informed by pain expertise as much as by organ-based medical knowledge. OBJECTIVE To summarise the evolving changes in the management of patients with chronic pelvic pain by referring to the 2012 version of the European Association of Urology (EAU) guidelines on chronic pelvic pain. EVIDENCE ACQUISITION The working panel highlights some of the most important aspects of the management of patients with chronic pelvic pain emerging in recent years in the context of the EAU guidelines on chronic pelvic pain. The guidelines were completely updated in 2012 based on a systematic review of the literature from online databases from 1995 to 2011. According to this review, levels of evidence and grades of recommendation were added to the text. A full version of the guidelines is available at the EAU office or Web site (www.uroweb.org). EVIDENCE SYNTHESIS The previously mentioned issues are explored in this paper, which refers throughout to dilemmas for the physician and treatment team as well as to the need to inform and engage the patient in a collaborative empirical approach to pain relief and rehabilitation. These issues are exemplified in two case histories. CONCLUSIONS Chronic pelvic pain persisting after appropriate treatment requires a different approach focussing on pain. This approach integrates the medical, psychosocial, and sexual elements of care to engage the patient in a collaborative journey towards self-management.

LONG-TERM RESULTS OF TRIGONE-PRESERVING ORTHOTOPIC SUBSTITUTION ENTEROCYSTOPLASTY FOR INTERSTITIAL CYSTITIS

PURPOSE Interstitial cystitis is a chronic debilitating condition mainly affecting women. Conservative treatment often produces unsatisfactory results and the identification of the best surgical treatment modality is difficult. We evaluate retrospectively the long-term results of trigone-preserving cystectomy followed by orthotopic substitution enteroplasty for women suffering from interstitial cystitis. MATERIALS AND METHODS The study comprised 18 women with a mean age of 55.9 years. All surgical interventions were performed by 1 surgeon. All patients completed a voiding log and were interviewed about symptoms. Renal ultrasonography was done to evaluate the upper urinary tract. Followup data also comprised blood chemistry studies, including vitamin B12 blood levels and blood gas analysis. Pain and lower urinary tract problems were measured using a validated self-assessment symptom index. RESULTS Ileocoecal augmentation was performed in 10 women and ileal substitute was done in 8. After a mean followup of 57 months 14 patients are completely pain-free, 12 void spontaneously and 15 report complete resolution of dysuria. Three patients perform intermittent self-catheterization and 1 woman prefers a suprapubic catheter for control of urinary hypercontinence. These 4 patients underwent ileoplasty. Surgery failed to relieve symptoms in 2 of the 18 patients. Surgery achieved a statistically highly significant improvement of diurnal and nocturnal voiding frequencies, functional bladder capacity and symptom index score. CONCLUSIONS Substitution enterocystoplasty is a valuable and safe therapeutic option for patients with intractable interstitial cystitis resistant to conservative therapy. In our series use of the ileocecal bowel segment showed better functional results.

Hyperthermia-Induced Proteasome Inhibition and Loss of Androgen Receptor Expression in Human Prostate Cancer Cells

Prostate cancer is the second leading cause of death in men in western countries and is usually treated by surgery and/or radiotherapy. More recently, hyperthermia has been introduced into clinical trials investigating a possible effect in the first-line treatment of prostate cancer. However, the molecular mechanisms of hyperthermia are not completely understood. In this study, we investigated the effects of hyperthermia on proteasome function and its significance for signal transduction, cell death and androgen receptor (AR) expression in PC-3, LnCaP, and DU-145 human and TRAMP-C2 murine prostate cancer cells. Hyperthermia caused apoptosis and radiosensitization and decreased 26S proteasome activity in all three human cell lines to about 40% of untreated control cells. 20S proteasome activity was not affected by heat. Heat treatment inhibited constitutive and radiation-induced activation of nuclear factor kappaB caused by stabilization of IkappaB. Although stabilization of AR by proteasome inhibitors has been reported previously, AR protein levels in LnCaP cells decreased dramatically after heat. Our data suggest that inhibition of proteasome function and dependent signal transduction pathways might be a major molecular mechanisms of heat-induced apoptosis and radiosensitization. Hyperthermia abrogates AR expression in androgen-dependent cells and might thus promote malignant progression of prostate cancer.

The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing radiation by a DNA-PK-independent mechanism

BackgroundBy modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition.MethodsProstate carcinoma PC-3 cells were treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution, apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were monitored. Radiosensitivity was assessed using a clonogenic assay.ResultsInhibition of proteasome function caused cell cycle arrest and apoptosis but this did not involve early activation of caspase-3. Short-time inhibition of proteasome function also caused radiosensitization but this did not involve a decrease in DNA-PKcs protein levels or DNA-PK activity.ConclusionWe conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132.