[Neuromodulation - new techniques]. / Neuromodulation - neue Techniken.

Neuromodulative procedures have become an inherent component in the therapy of functional urinary bladder and pelvic floor function disorders. Sacral neuromodulation has been used in Germany for more than 20 years and reresents the standard neuromodulative therapy. Technical improvements in the field of test stimulation and the phasing out of the large pulse generator models represent current changes with the resulting advantages and disadvantages. Pudendal neuromodulation (PNM) has been known for many years as a procedure for treatment of chronic diseases of the urinary bladder and the lesser pelvis and is predominantly used as second-line neuromodulative therapy; however, for pelvic pain syndromes and in particular for pudendal neuralgia, it represents a promising minimally invasive first-line therapy. Due to the technically demanding puncture procedure, PNM has so far only been used in Germany in specialized centers. Through the development of new operation techniques, the prerequisites for a wider multicentric use, with the future aim of approval of the procedure, have been achieved. External transdermal pudendal neuromodulation is a promising therapeutic approach and after further testing in randomized studies could find an application as a conservative step before minimally invasive pudendal neuromodulation. Although the technique of laparoscopic electrode placement on neural structures of the lesser pelvis is technically attractive, it predominantly finds a monocentric use and must in due course be critically compared with established minimally invasive procedures.

[Management of chronic metabolic acidosis in neobladder patients: survey among urologists regarding diagnosis and therapy]. / Chronische metabolische Azidose bei Neoblasepatienten : Umfrage zu Diagnose und Therapie.

BACKGROUND: The guideline of the "Deutsche Gesellschaft für Urologie" recommends capillary blood gas analysis for neobladder patients every 3 months. In case of chronic metabolic acidosis (CMS), treatment with oral bicarbonate is recommended. However, it is unknown how these recommendations are implemented in daily practice. OBJECTIVES: The aim of this study was to evaluate the current diagnosis, rating and therapy of CMA among neobladder patients by German urologists. MATERIALS AND METHODS: A survey covering diagnosis, rating, and therapy of CMA was sent to 5,539 urologists in Germany in August 2013. All 350 (6.3%) completed surveys were analyzed. RESULTS: Nearly all respondents (98%) perform blood gas analysis (BGA) to diagnose CMA, usually following unspecific symptoms such as general discomfort and fatigue. In addition, about half of the urologists frequently check their neobladder patients for CMA, regardless of any symptoms. The incidence of CMA directly following neobladder construction was estimated to be 64%. Approximately 17% of all patients need permanent CMA treatment. Ninety nine percent of all respondents prefer to treat CMA with oral bicarbonate at a daily dose of 1000-3000 mg, mostly with enteric coated formulations. CONCLUSION: CMA is an important comorbidity after neobladder construction. Furthermore, the respondents of the survey expressed great interest in receiving medical education regarding the management of CMA in neobladder patients.

Comparative pilot study of implantation techniques for pudendal neuromodulation: technical and clinical outcome in first 20 patients with chronic pelvic pain.

PURPOSE: Neurostimulation of the pudendal nerve (PN) is considered for patients who have failed sacral neuromodulation. Previous techniques for PN localization are described to be uncomplicated and promise to achieve accuracy in electrode placement. However, in clinical use, they appear challenging. We developed a puncture technique using fixed anatomical landmarks for a fast and reproducible localization of the PN. METHODS: Full-body cadavers and dissected anatomical preparations were studied for the course of the PN. Fluoroscopically controlled fixed anatomical landmarks locating the pudendal trunk were defined. Lead placement following established techniques was performed, and the topographic relationship to the PN was documented by dissection. In a pilot series of 20 patients with chronic pelvic pain, pudendal neuromodulation (PNM) was performed uni- and bilateral using the different approaches. Technical and clinical outcomes of the various techniques were compared. RESULTS: Fixed anatomical landmarks such as ischial spine, ischial tuberosity, acetabulum and anal rim resulted in a right-angled triangle with a new start and target point for puncture. Initials of the landmarks add up to the teaching acronym STAR. STAR technique including a puncture angle of 60° and a gluteal lead exit places 3-4 electrode poles at the nerve. In clinical trial, mean operation time for bilateral PNM in STAR was 85 min with mean puncture attempts of 3.5 to reach the nerve. Pain decreased statistically significant only in bilateral PNM. CONCLUSIONS: The STAR approach appears to achieve technical standardisation and optimized reproducibility in pudendal lead placement resulting into an increased feasibility of PNM.

[Neuralgia of the pudendal nerve following violent trauma: analgesia by pudendal neuromodulation]. / Nervus-pudendus-Neuralgie infolge Gewalttrauma : Schmerzlinderung durch pudendale Neuromodulation.

Pudendal neuralgia is a neuropathic disease which is predominantly caused by pelvic trauma with pressure or stretching strain of the pudendal nerve. The Nantes criteria are used for the differential diagnostics of this disease and therapy includes pressure-relieving and analgesic measures using laparoscopic or open decompression procedures. This article reports the case of a female patient who developed pudendal neuralgia following violent trauma to the pelvic and urogenital regions. Due to the complexity of the symptoms combined sacral and pudendal neuromodulation (PNM) was carried out. A direct comparison of neuromodulative techniques revealed that PNM was superior resulting in almost complete freedom from pain. The PNM procedure could represent a therapeutic option for treatment of pudendal neuralgia.

[The future of invasive neuromodulation: new techniques and expanded indications]. / Die Zukunft der invasiven Neuromodulation : Neue Techniken und erweiterte Indikationen.

Due to the increasing popularity of neuromodulation, the number of indications and patient groups to which this technique is offered is also increasing. We evaluated the currently available data concerning neuromodulation in geriatric patients, children and patients with spinal cord injury and potential alternatives regarding neural targets and implantation techniques.The evidence of the use of neuromodulation in these patient groups is low. In geriatric patients, the use of neuromodulation seems to be justified. The few existing results concerning neuromulation in children are positive; however, there are no data about long term effects of neuromodulation on the growing organism. In patients with spinal cord injury, neuromodulation by microsurgical nerve anastomosis does not seem to be successful. According to the preliminary data of a single study, neuromodulation in acute spinal cord injury may prevent development of a neurogenic bladder dysfunction. The laparoscopic implantation of electrodes for neuromodulation unfolds new technical opportunities; however, until today there is no proof of the efficacy of this technique. Pudendal neuromodulation appears to be a meaningful addition to the therapeutic armamentarium for selected indications.The existing studies demonstrate the future opportunities of neuromodulation also in geriatric patients, children and patientens with spinal cord injuries. However, especially in the latter two groups, further studies concerning effectiveness and long term consequences are mandatory prior to offering these techniques to patients in everyday practise.

[Bladder dysfunction caused by a large presacral retention mucocele]. / Blasenfunktionsstörung in Folge einer grossen präsakralen Retentionsmukozele.

Large pelvic masses can displace the urinary bladder and cause bladder dysfunction with various symptoms. We report the case of a 42-year-old man who described a feeling of reduced urinary stream and bladder filling and residual urine since his youth. After various unsuccessful conservative treatments, the patient was evaluated by our neuro-urologic department. The diagnostic workup revealed a large cystic mass that displaced the urinary bladder. Histopathological examination showed a retention mucocele (the patient had been surgically treated for connatal anal atresia). The lesion was surgically excised.

Long-term results of amitriptyline treatment for interstitial cystitis.

PURPOSE: We have conducted a prospective open-label study to examine the safety and efficacy of the long-term administration of the tricyclic antidepressant amitriptyline in patients with interstitial cystitis (IC). METHODS: Patients were stratified into 2 groups: an NIDDK group including patients fulfilling the NIDDK criteria for IC and a non-NIDDK group encompassing patients who presented the characteristic IC symptoms but met at least one of the NIDDK exclusion criteria. Amitriptyline was taken strictly at bedtime following an established self-titration protocol without a limitation of the maximum daily dosage. Patients reporting improvement in a global response assessment questionnaire were defined as treatment responders. Further efficacy measures included changes of pain and urgency, functional bladder capacity and frequency. Changes in the O'Leary-Sant IC index and rating of overall satisfaction with the therapeutic outcome are reported as well. RESULTS: The mean follow-up of the study was 19.0 +/- 12.5 months. The response rate was 64% (60 patients). Overall mean dosage was 55 mg (range: 12.5-150 mg). Side effects occurred in 79 patients (84%) (dry mouth: 79%, weight gain: 59%). Patient overall satisfaction with the therapeutic result was either excellent or good in 43 patients (46%). The drop-out rate was 31% (29 patients) after a mean treatment period of 6 weeks at a mean dosage of 70 mg. Non-response to treatment was the primary reason for drop-out in all cases, side effects contributed to drop-out in 25 patients (86%). The various IC symptoms improved statistically significant compared with baseline. CONCLUSIONS: Long-term administration of amitriptyline is a feasible, safe and effective treatment for IC provided that the drug is used judiciously to minimise adverse effects. The therapeutic response to amitriptyline was uniformly observed in patients fulfilling the NIDDK criteria and in those patients with the pure clinical diagnosis of IC.

[From end-organ disease to a classifiable bladder pain syndrome: paradigm shift in the understanding of urological pain syndromes exemplified by the condition currently called interstitial cystitis]. / Von der Endorganerkrankung zum klassifizierbaren Blasenschmerzsyndrom: Paradigmenwechsel im Verständnis urologischer Schmerzsyndrome am Beispiel der interstitiellen Zystitis.

Growing clinical and scientific data imply that the condition currently called interstitial cystitis is not just a mere bladder end-organ disease but that the symptoms perceived to be related to the bladder are rather one aspect of a complex pelvic pain syndrome. The term bladder pain syndrome/interstitial cystitis (BPS/IC) suggested by the European Society for the Study of IC/PBS (ESSIC) for this condition is currently the only one strictly consistent with the taxonomy guidelines of the European Association of Urology and the International Association for the Study of Pain. BPS would be diagnosed on the basis of chronic pelvic pain, pressure, or discomfort perceived to be related to the urinary bladder, accompanied by at least one other urinary symptom such as persistent urge to void or urinary frequency. Confusable diseases as the cause of the symptoms must be excluded. Classification of BPS types might be performed according to findings at cystoscopy with hydrodistention and morphologic findings in bladder biopsies. The end-organ condition interstitial cystitis has thus become a chronic pain syndrome with a predominantly neurovisceral pathophysiology. In daily practice, therapeutic approaches aiming at both the peripheral bladder urothelium and central nervous targets should be combined. A multimodal treatment strategy, such as the combination of tricyclic antidepressants with instillation therapy, still appears reasonable and justified.

[The complexity of chronic pelvic pain exemplified by the condition currently called interstitial cystitis. Part 2: Treatment]. / Die Komplexität chronischer Beckenschmerzen am Beispiel der Interstitiellen Zystitis. Teil 2: Therapie.

The so-called interstitial cystitis is a chronic pain syndrome rather than a purely end organ disease of the urinary bladder. New suggestions for definitions and nomenclature take this into consideration. Since aetiology and pathogenesis are still unknown a treatment of the cause is still not possible. There are neither evidence-based treatment algorithms nor a so-called standard therapy. Numerous therapeutic approaches have been tried up to now. These attempts can be divided into oral, intravesical, surgical and physical procedures. There are also meaningful supplementary therapy procedures beyond the boundaries of classical school medicine. The WHO staging scheme provides the basis for every pain therapy. For the oral therapeutic procedures in current use the following medications with differing levels of evidence have been recommended: amitriptylin, hydroxyzin, pentosan polysulfate. Many other orally administered drugs have also been used although in many cases evidence of efficacy is lacking, these included anticonvulsants, L-arginine and various immunomodulators and immunosuppressants. Among the intravesical therapeutic procedures botulinum toxin A, dimethyl sulfoxide, heparin and glycosaminoglycan substitutes have been used. For the physical procedures, besides bladder distension, hyperbaric oxygen therapy shows efficacy. When the conventional therapeutic methods fail, surgical (partial) removal of the urinary bladder or urinary diversion procedures represent the therapeutic ultimo ratio. There are hardly any controlled studies on alternative curative procedures although rather good results have been obtained in chronic pelvic pain syndrome with acupuncture as an additional therapeutic modality.

[The complexity of chronic pelvic pain exemplified by the condition currently called interstitial cystitis. Part 1: Background and basic principles]. / Die Komplexität chronischer Beckenschmerzen am Beispiel der Interstitiellen Zystitis. Teil 1: Theoretische Grundlagen.

The so-called interstitial cystitis is a chronic pain syndrome rather than a purely end organ disease of the urinary bladder. New suggestions for definition and nomenclature take this into consideration. Since aetiology and pathogenesis are still unknown a causal treatment is still not at hand. There are neither evidence-based treatment algorithms nor a so-called standard therapy. Numerous therapeutic approaches have been tried up to now. These attempts can be divided into oral, intravesical, surgical and physical procedures. There are also meaningful supplementary therapy procedures beyond the boundaries of classical school medicine. The WHO guidelines provide the basis for every pain therapy. For the oral therapeutic procedures in current use the following medications with differing levels of evidence have been recommended: amitriptylin, hydroxyzin, pentosan polysulfate. Many other orally administered drugs have also been used although in many cases evidence of efficacy is lacking, these included anticonvulsants, L-arginine and various immunomodulators and immunosuppressants. Among the intravesical therapeutic procedures botulinum toxin A, dimethyl sulfoxide, heparin and glycosaminoglycan substitutes have been used. For the physical procedures, besides bladder distension, hyperbaric oxygen therapy shows efficacy. When conventional therapeutic methods fail, surgical (partial) removal of the urinary bladder or urinary diversion procedures represent the therapeutic ultimo ratio. There are hardly any controlled studies on alternative curative procedures although rather good results have been obtained in chronic pelvic pain syndrome with acupuncture as an additional therapeutic modality.

[Interstitial cystitis. An important differential diagnosis]. / Interstitielle Zystitis. Eine wichtige Differentialdiagnose.

Interstitial cystitis (IC) is a chronic, debilitating inflammatory disease of the urinary bladder, characterized by chronic pelvic pain, urgency/frequency symptoms, and decrease of the functional bladder capacity. Both the etiology and pathogenesis of the condition that predominantly affects women are still not fully understood. Thus, a causal therapeutic approach still does not exist. IC remains a strict diagnosis of exclusion; distinct histopathological findings within the bladder wall are frequently found, although they are not pathognomonic. The diagnostic criteria elaborated by the NIH are helpful in clinical research; their dogmatic utilization will however lead to an underdiagnosis of IC in 60% of the patients. IC-specific symptom questionnaires and validated symptom scales help the physician to assess the therapeutic response during the follow-up of the patients.

Androgen deprivation induces selective outgrowth of aggressive hormone-refractory prostate cancer clones expressing distinct cellular and molecular properties not present in parental androgen-dependent cancer cells.

PURPOSE: The mechanism of progression of human prostate cancer (CaP) cells under androgen ablation therapy remains unclear. To study the alternative pathways of CaP cell growth under conditions of androgen deprivation, androgen-independent CaP variants were selected and expanded from an androgen-dependent CaP line via an in vitro androgen deprivation treatment. Cellular and molecular properties of these androgen-independent variants were characterized both in vitro and in vivo and compared with those of their parental androgen-dependent cells. METHODS: Androgen deprivation treatment of an androgen-dependent CaP cell line, LNCaP, was carried out by replacing culture medium with RPMI 1640 medium plus 10% charcoal-stripped serum. Cells that survived through the androgen deprivation treatment were harvested and expanded in the androgen-deficient culture medium and were designated CL-1. The CL-1 cells were also recultured in androgen-containing medium and designated CL-2. The growth (cell cycle analysis, 3H-thymidine incorporation assay, growth expansion, and colonization efficiency), expression of CaP-associated markers (semiquantitative reverse transcriptase polymerase chain reaction), interaction with endothelial and bone marrow stromal cells, sensitivity to anticancer agents and radiation (growth inhibition), and tumorigenicity of CL-1 and CL-2 cells were determined and compared with these characteristics in parental LNCaP cells. RESULTS: CL-1 and CL-2 cells are fast-growing cells when compared with parental LNCaP cells. They were capable of potentiating the growth of endothelial and bone marrow stromal cells in co-culture experiments and acquired significant resistance to radiation and to anticancer cytotoxic agents (Taxol paclitaxel, vinblastine, and etoposide). In contrast to the poorly tumorigenic parental LNCaP cells, CL-1 and CL-2 lines proved highly tumorigenic, exhibiting invasive and metastatic characteristics in intact and castrated mice or in female mice within a short period of 3 to 4 weeks. No growth supplements (e.g., Matrigel) were needed. When transfected with the green fluorescence protein (GFP) gene and transplanted orthotopically in the accessory sex gland, extensive metastatic disease from the primary CL tumor could be identified in bone, lymph nodes, lung, liver, spleen, kidney, and brain. Semiquantitative reverse transcriptase polymerase chain reaction analysis revealed a markedly distinct molecular expression profile in the CL lines: overexpression of basic fibroblast growth factor, interleukin-6, interleukin-8, vascular endothelial growth factor, transforming growth factor-beta, epidermal growth factor receptor, caveolin, and bcl-2 messenger RNAs and marked down-regulation of E-cadherin, p-53, and pentaerythritol tetranitrate. CONCLUSIONS: Early administration of hormonal therapy after failure of first-line treatment is associated with a profound clonal selection of aggressive AI variants, such as CL-1 and CL-2 lines. These tumor lines, with their parental counterparts, can serve as valuable tools for studying the cellular and molecular mechanisms of CaP progression and metastasis under hormonal therapy. CL-1 and CL-2 offer a unique and reproducible model for the evaluation of drug sensitivity and for other therapeutic modalities for advanced prostate cancer.

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 of removing a urethral foreign body depends on the size and mobility of the object applied to the genitourinary tract. When possible, endoscopic and minimal invasive techniques of removal should be used. However, surgical retrieval of a foreign body may be required, particularly when there is a severe associated inflammatory reaction.

[Diagnosis of interstitial cystitis]. / Diagnostik der interstitiellen Zystitis.

Interstitial cystitis (IC) represents a rare and complex inflammatory bladder condition in which diagnostics can be challenging. Strict NIH criteria for its diagnosis were designed for research purposes. Their routine application would miss large proportions of IC patients. When IC is suspected, history and physical exam are followed by an evaluation of long-term voiding diaries. Large voided volumes (functional capacity > 250 cc) or longer micturition intervals (> 2 h.), absence of nocturia or symptom-free periods reduce the likelihood of IC. Further exclusion diagnostics include urine tests (infection), cytology (in-situ carcinoma), ultrasound (calculi, bulks, anomalies) and urodynamics in selected cases. Bladder capacity measurements under sedoanalgesia are of limited value, since functional low-volume bladders can be mechanically extendable. Cystoscopy under general anesthesia represents the diagnostic standard procedure for IC during which 90% of IC-patients present with characteristic mucosal glomerulations after bladder distension. Biopsies are recommended for exclusion of malignancy. Potassium-leak testing plays no relevant role in routine diagnostics due to its poor sensitivity. Similarly, complex determinations of novel IC markers (histamine, tryptase, cytokines, growth factors, substance P, nitric oxide) are of no relevance in clinical settings and should be restricted to research projects.

[Open surgical therapy of interstitial cystitis]. / Offen-chirurgische Therapie der interstitiellen Zystitis.

Treatment of IC is one of the most difficult therapeutic challenges in urology, frequently resulting in frustration for both patient and therapist. Many urologists believe that conservative treatment should not be unnecessarily prolonged in severe cases with low bladder capacity, since cystectomy may provide immediate and permanent relief for the suffering patient. However, it remains unclear which surgical approach and technique is the most suitable. Generally three different techniques are performed: supratrigonal cystectomy; radical cystectomy, saving only the bladder neck; and, finally, radical cystectomy combined with excision of the urethra. All three techniques require substitution of the excised bladder tissue with bowel segments.

Current Status of Partial Nephrectomy in the Management of Kidney Cancer.

BACKGROUND: The technique of partial nephrectomy for managing renal cancers is well recognized, but guidelines regarding indications for its use are not generally accepted. METHODS: The authors review the indications for partial nephrectomy in various clinical situations, and they include their own experience to clarify the utility of the technique. RESULTS: Intraoperative renal ultrasound and helical computed tomography can assist the surgeon in technical decisions. Partial nephrectomy is considered when nephrectomy would render the patient anephric and dependent on dialysis. CONCLUSIONS: The technical and operative advances in partial nephrectomy make the approach increasingly attractive for patients with kidney cancer in a variety of clinical circumstances.