Thilo Schwalenberg

Anxiety and depression in patients with prostate cancer and other urogenital cancer: A longitudinal study

OBJECTIVE The aim of this study was to assess the degree and the course of psychological distress (anxiety and depression) in cancer patients and to detect sociodemographic determinants of the scores. METHODS AND MATERIALS Patients with prostate cancer (n = 287) and other urogenital cancer (n = 126) were tested with the Hospital Anxiety and Depression Scale (HADS) at the following time points: at the beginning (T1) and the end (T2) of the treatment in the hospital, 6 months later (T3), and 1 year later (T4). RESULTS Anxiety mean scores were highest at the start of the stay in the hospital. About 36% of the patients were at least doubtful cases at T1. However, the anxiety mean scores from T2 to T4 were similar to those of the general population and lower than those of cardiac patients. Depression mean scores were even lower than those of the general population. Young age and receiving radio- and/or chemotherapy were predictive of higher psychological distress. CONCLUSIONS The low mean scores of anxiety and depression from T2 to T4 indicate that most of the prostate cancer patients do not need help from mental health professionals. Nevertheless, some patients may profit from mental health support, especially at the beginning of the stay in the hospital.

Intravesical treatments of bladder pain syndrome/interstitial cystitis

Bladder pain syndrome/interstitial cystitis (BPS/IC) is a disabling chronic condition that affects up to 7% of women in the USA. In men, BPS/IC seems to be less common, but might be underestimated because it can be confused with chronic prostatitis. The aetiology and pathophysiology of BPS/IC are not well understood. Consequently, diagnosis and treatment is challenging and most therapies used to date are off-label. These therapies include bladder instillation with dimethyl sulfoxide (DMSO) and BCG, as well as hyperbaric oxygen therapy. Overall, botulinum neurotoxin A injection, intravesical sodium hyaluronate instillation and DMSO instillation seem to be the best-performing treatments, with response rates of 79%, 76% and 75%, respectively, and can be used effectively as second-line or third-line therapies for BPS/IC. However, additional high-quality randomized controlled trials are necessary to improve the available data.

TGF-β1 Inhibits Cx43 Expression and Formation of Functional Syncytia in Cultured Smooth Muscle Cells from Human Detrusor

BACKGROUND Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. OBJECTIVE In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. DESIGN, SETTING, AND PARTICIPANTS hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. MEASUREMENTS Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. RESULTS AND LIMITATIONS Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. CONCLUSIONS Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

The relationship of quality of life and distress in prostate cancer patients compared to the general population

Background: The aim of this study is two-fold. The first part compares quality of life (QoL) data of prostate cancer patients with those of a representative and age-specific sample of the general population and analyzes the influence of cancer related as well as socio-demographic parameters on QoL. Secondly, differences in QoL depending on the experienced psychological distress will be shown both in prostate cancer patients and in the general population. Material and Methods: A sample of 265 prostate cancer patients completed both the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Hospital Anxiety and Depression Scale (HADS) during their stay in the hospital. A total HADS cut off score of 15 was used to indicate psychological distress and significant emotional concerns in patients and men of the general population. The results of the patients were compared with those of the general population (N=444). Results: Prostate cancer patients reported significantly worse levels of social and emotional functioning as well as more symptoms like insomnia, constipation and diarrhea compared to the general population. Patients and men of the general population with a total HADS score ≥15 reported lower QoL in all sub-scales except for diarrhea in comparison to people without distress. Discussion: Psychological distress is accompanied by lower QoL and therefore should be taken into consideration when QoL is assessed. Furthermore, clinicians should be trained by professionals to detect distress in their patients and to pay more attention to their emotional concerns, which are strongly associated with the patients’ well-being and QoL during their stay in hospital.

Is the Male Dog Comparable to Human? A Histological Study of the Muscle Systems of the Lower Urinary Tract

Because of their superficial anatomical resemblance, the male dog seems to be suitable for studying the physiologic and pathological alterations of the bladder neck of human males. The present study was carried out to compare and contrast the muscular anatomy of the male dog lower urinary tract with that of humans. The complete lower urinary tract, including the surrounding organs (bulb of penis, prostate, rectum and musculature of the pelvic floor) were removed from adult and newborn male dogs and histologically processed using serial section technique. Based on our own histological investigations, three‐dimensional (3D)‐models of the anatomy of the lower urinary tract were constructed to depict the corresponding structures and the differences between the species. The results of this study confirm that the lower urinary tract of the male dog bears some anatomical resemblance (musculus detrusor vesicae, prostate, prostatic and membranous urethra) to man. As with human males, the two parts of the musculus sphincter urethrae (glaber and transversostriatus) are evident in the canine bladder neck. Nevertheless, considerable differences in formation of individual muscles should be noted. In male dogs, no separate anatomic entity can be identified as vesical or internal sphincter. The individual course of the ventral and lateral longitudinal musculature and of the circularly arranged smooth musculature of the urethra is different to that of humans. Differences in the anatomy of individual muscles of the bladder neck in the male dog and man suggest that physiological interpretations of urethral functions obtained in one species cannot be attributed without qualification to the other.

Neuroanatomy of the male pelvis in respect to radical prostatectomy including three-dimensional visualization

The neuroanatomical structures of the radical prostatectomy (RP) are extensively discussed for their existence, localization and function. Especially structures, e.g. the so‐called neurovascular bundle (NVB) that are points of debate in numerous anatomical studies. We review the literature and present our observations in cadaveric specimens, to reconstruct neuroanatomical structures in three dimensions (3D) with the use of appropriate computer applications and produce images of operative fields. We used an internet PubMed survey (http://www.ncbi.nlm.nih.gov) to review recent publications and included back copies of historical neuroanatomical studies from our own library. Our own experimental cadaveric (specimens preserved in Thiel’s solution) studies of the autonomic nerve supply of the lower urinary tract were also reviewed. Visualization of the pelvic anatomy and neuroanatomy was done using computer‐based software packages. No unified terminology for the structures of the NVBs can be presented to date. The innervation of the smooth muscular structures of the urethra and the complex morphology of urethral sphincter remain unclear. Our cadaveric studies showed that nerves are located on the lateral aspect of the prostate in addition to the NVBs described at the dorsolateral side of the prostate. The neuroanatomical investigations of the male pelvis and visualization of the structures in 3D enable the presentation of operative sites as seen intraoperatively. Moreover, dynamic depiction of the pelvic floor is also possible.

Health-related quality of life of prostate cancer patients compared to the general German population: age-specific results.

Objective: The objective of this study was to examine the age-specific health-related quality of life (HRQOL) of prostate cancer patients (PCPs). Patients and Methods: 387 PCPs were asked to self-assess their HRQOL with the EORTC QLQ-C30 questionnaire. Patients’ data were compared with those of the general German population. Results: The reported global health/QOL scores of the study group and the general German population are nearly equal. However, most of the subdomains of HRQOL are negatively affected in PCPs, especially in younger patients (≤59 years). Conclusion: Medical professionals should pay more attention to the emotional burden of PCPs, because their stress and strains during the time before treatment have a rather more emotional than physical character.

Colon pouch (Mainz III) for continent urinary diversion

Authors from Germany present data on the Mainz III pouch, where a colon segment is used. The results were very encouraging, with excellent continence rates. They suggest that this technique of continent urinary diversion should be considered as a suitable alternative to other methods.

Struktur und Funktion der suburothelialen Myofibroblasten in der humanen Harnblase unter normalen und pathologischen Bedingungen

BACKGROUND Myofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders. PATIENTS AND METHODS Bladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells. RESULTS Myofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes. CONCLUSIONS Upregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the etiology of urge incontinence. A multi-step model is presented as a working hypothesis.ZusammenfassungHintergrundBei zahlreichen pathologischen Veränderungen spielen Myofibroblasten eine wesentliche Rolle. Die Aufklärung der Struktur und Funktion sowie der zellulären Plastizität dieses Zelltyps in der Harnblase könnte zu einer neuen Beurteilung der Pathogenese von Harnabflusstörungen führen.Patienten und MethodenHarnblasenbiopsien von Tumorpatienten und Patienten mit interstitieller Zystitis wurden immunhistologisch und elektronenmikroskopisch untersucht. Kopplungseigenschaften wurden an kultivierten Myofibroblasten und Detrusormuskelzellen mit Hilfe von Farbstoffinjektion analysiert.ErgebnisseMyofibroblasten stehen in engem Kontakt zum suburothelialen Kapillarnetz. Sie exprimieren Cx43 und bilden funktionelle Synzytien. Die Expression von muskarinischen und purinergen Rezeptoren variiert sehr stark. In Farbstoffkopplungsexperimenten fanden wir Unterschiede zu Detrusormyozyten.DiskussionPathologische Expression von glattmuskulärem Aktin und/oder Transdifferenzierung zu glatten Muskelzellen könnten eine Rolle bei der Ätiologie der Dranginkontinenz spielen. Ein mehrstufiges Modell wird als Arbeitshypothese vorgeschlagen.AbstractBackgroundMyofibroblasts play a pivotal role in numerous pathological alterations. Clarification of the structure and function and of the cellular plasticity of this cell type in the bladder may lead to new insights into the pathogenesis of lower urinary tract disorders.Patients and methodsBladder biopsies from patients with bladder carcinoma and interstitial cystitis were used to analyse the morphology and receptor expression using confocal immunofluorescence and electron microscopy. Cytokine effects and coupling behavior were tested in cultured myofibroblasts and detrusor smooth muscle cells.ResultsMyofibroblasts are in close contact with the suburothelial capillary network. They express Cx43 and form functional syncytia. The expression of muscarinic and purinergic receptors is highly variable. Dye coupling experiments showed differences to detrusor myocytes.ConclusionsUpregulation of smooth muscle cell alpha-actin and/or transdifferentiation into smooth muscle cells may contribute to the ethiology of urge incontinence. A multi-step model is presented as a working hypothesis.

Histamine receptors in human detrusor smooth muscle cells: physiological properties and immunohistochemical representation of subtypes

The potent inflammatory mediator histamine is released from activated mast cells in interstitial cystitis (IC). Here, we report on the histamine receptor subtypes involved in the intracellular calcium response of cultured smooth muscle cells (cSMC). Fura-2 was used to monitor the calcium response in cSMC, cultured from human detrusor biopsies. The distribution of histamine receptor subtypes was addressed by immunocytochemistry in situ and in vitro. Histamine stimulated a maximum of 92% of the cells (n=335), being more effective than carbachol (70%, n=920). HTMT (H1R-agonist), dimaprit (H2R) and MTH (H3R) lead to significant lower numbers of reacting cells (60, 48 and 54%). Histamine receptor immunoreactivity (H1R, H2R, H3R, H4R) was found in situ and in vitro. Histamine-induced calcium increase is mediated by distinct histamine receptors. Thus, pre-therapeutic evaluation of histamine receptor expression in IC patients may help to optimize therapy by using a patient-specific cocktail of subtype-specific histamine receptor antagonists.