Removal of Common Bile Ducts Stones via Percutaneous Access with a Flexible Ureteroscope and Laser Assistance.

Two patients are described with large stones in the common bile duct. Standard ERCP was not possible. Both patients were successfully treated with percutaneous access and use of the ureteroscope with the holmium laser.

Gene-expression signature of adhesion/growth-regulatory tissue lectins (galectins) in transitional cell cancer and its prognostic relevance.

AIMS: Lectins, and especially galectins, appear to be important in malignancy-associated processes. The aim was to analyse comprehensively the presence of galectins in urothelial tumours. METHODS AND RESULTS: Non-cross-reactive antibodies against seven family members from the three subgroups (prototype: galectin-1, -2 and -7; chimera type: galectin-3; tandem-repeat type: galectin-4, -8 and -9) were used. Gene expression was monitored in specimens of normal urothelium, fresh tumour tissue and cell lines by real-time polymerase chain reaction (PCR). The presence and evidence of tumour-associated up-regulation were shown for galectin-1 and -3. This was less clear-cut for galectin-4 and -8. Galectin-7 was expressed in all cell lines; galectin-2 and -9 were detected at comparatively low levels. Galectin-2, -3 and -8 up-regulation was observed in superficial tumours, but not in muscle-invasive tumours (P < 0.05). Immunoreactivity correlated with tumour grading for galectin-1, -2 and -8, and disease-dependent mortality correlated with galectin-2 and -8 expression. Binding sites were visualized using labelled galectins. CONCLUSIONS: The results demonstrate a complex expression pattern of the galectin network in urothelial carcinomas. Galectin-1, -2, -3 and -8 are both potential disease markers and also possible targets for bladder cancer therapy.

Construction and characterization of efficient, stable and safe replication-deficient foamy virus vectors.

As serious side effects affected recent virus-mediated gene transfer studies, novel vectors with improved safety profiles are urgently needed. In the present study, replication-deficient retroviral vectors based on feline foamy virus (FFV) were constructed and analyzed. The novel FFV vectors are devoid of almost the complete env gene plus the internal promoter - accessory bel gene cassette including the gene for the viral transcriptional transactivator Bel1/Tas. In these Bel1/Tas-independent vectors, expression of the lacZ (beta-galactosidase) marker gene is directed by the heterologous, constitutively active human ubiquitin C promoter (ubi). Env-transcomplemented vectors have un-concentrated titers of more than 10(5) transducing units/ml. The vectors allow efficient transduction of a broad array of diverse target cells, which can be increased by repeated vector exposure. However, the number of lacZ marker gene expressing cells decreased slightly upon serial passages of the transduced cells. Vectors carrying a self-inactivating (SIN) deletion of the TATA box and most parts of the viral promoter were not rescued by wt FFV whereas those with the intact or a partially deleted promoter were readily reactivated. This finding indicates that the viral promoters are in fact non-functional, pointing to a highly advantageous safety profile of these new FFV-ubi-lacZ-SIN vectors.

[Nephropexy in the course of time. Aspects of an historical surgical technique]. / Die Nephropexie im Wandel der Zeit. Aspekte einer historischen Operationstechnik.

The first successful nephropexy was performed in the year 1881. From this time, surgical therapy of nephroptosis has always been a subject of discussion. A partly uncritical acceptance led to nephropexy being the most performed urological operation at the beginning of the 20th century, with up to 200 different surgical variations. As early as the 15th century, a first description of ren mobilis was made by Alessius de Pedemontanus. The first surgical intervention for the treatment of nephroptosis was performed by Gilmore in 1870. In 1877, the American Dowell from New Orleans tried a fixation of the kidney through a seton, however, this operation failed. Eventually in 1881, Eugen Hahn from Berlin was able to perform the first successful nephropexy, he named this method "nephroraphy". In 1882, the first modification was made by Bassini with sutures through the renal capsule. Finally, the gynaecologist George Edebohl led nephropexy into a great popularity and secured the method through numerous technical innovations. By 1936, approximately 170 different surgical methods existed for fixation of the kidney. An accurate diagnosis is imperative before performing nephropexy. There were times in which this operation was carried out much too often and, therefore, had a bad reputation. However, it is not correct to drop nephropexy altogether as some would prefer. The statement by Professor Voelcker from Halle in the year 1911 that for all those who have a urinary obstruction and those with a beginning dilation, nephropexy is still justified and may - when correctly performed provide many blessings". Nothing needs to be added to this.

Hans Christian Jacobaeus: Inventor of human laparoscopy and thoracoscopy.

Hans Christian Jacobaeus performed the first clinical laparoscopic surgery in Stockholm. This pioneering procedure was based on the animal experiments of Georg Kelling (1866-1945), a German physician from Dresden, who performed the first laparoscopic intervention in 1901 using a Nitz cystoscope in a dog. In 1910, Jacobaeus published his initial experiences with laparoscopic surgery in the Münchner Medizinischen Wochenschrift under the title "The Possibilities for Performing Cystoscopy in Examinations of Serous Cavities." He used this technique for diagnostic purposes in undefined abdominal complaints and functional impairment. Jacobaeus was the first who pointed out the possibility of injuring organs, especially the intestines, by inserting the trocar. In 1910, Jacobaeus recognized the immense diagnostic and therapeutic possibilities of laparoscopic surgery, as well as its difficulties and limits. He also was the first to realize the need for initial endoscopic training in animals and corpses. He promoted the development of special laparoscopic instruments to optimize and simplify the procedure.

[Malignant mesothelioma of the testes]. / Das maligne Mesotheliom des Hodens.

INTRODUCTION: Malignant mesothelioma of the tunica vaginalis is a very rare malignant tumour. The prevalence of mesothelioma is about 1 : 1 000 000: Only 1 % have their origin in the tunica vaginalis testis with a 5-year survival of less than 5 %. About 80 cases have been reported in the literature. In 41 % of these cases exposure to asbestos for many years was determines. CASE REPORT: We report on a 76-year-old patient who presented with an atypical hydrocele testis. Intraoperatively, thickened testicular walls and an crystalline lawn adjacent to the tunica vaginalis testis were found. CONCLUSIONS: Ultrasonography showing snow flurries together with cloudy hydrocele fluid and visible crystal particles and thickened testicular walls may help to identify a mesothelioma of the testicular walls. Intraoperative frozen section and a high inguinal orchiectomy is the operative method of choice.

[Hans-Christian Jacobaeus (1879-1937): The inventor of human laparoscopy and thoracoscopy]. / Hans-Christian Jacobaeus (1879-1937) : Die erste Laparoskopie und Thorakoskopie beim Menschen.

Already 94 years ago in 1910, Dr. Hans Christian Jacobaeus performed the first clinical laparoscopic surgery in Stockholm. His pioneering procedure was based on the animal experiments of Georg Kelling (1866-1945), a German physician from Dresden, who performed the first laparoscopic intervention in 1901 using a Nitze cystoscope in a dog. In 1910 Jacobaeus published his first experiences with laparoscopic surgery in the Münchner Medizinische Wochenschrift under the title "The possibility to perform cystoscopy in examinations of serous cavities." He used this technique for diagnostic purposes in unclear abdominal complaints and functional impairment. Jacobaeus was the first who pointed out the possibility of causing injury to organs, especially the gut, by inserting the trocar. In 1910 Jacobaeus recognized the immense diagnostic and therapeutic possibilities of laparoscopic surgery, but also the difficulties and limits. He also was the first who recognized the need to complete training sessions on animals and corpses. He demanded the development of special laparoscopic instruments to optimize and simplify the operation.

[Georg Kelling (1866-1945): the man who introduced modern laparoscopy into medicine]. / Georg Kelling (1866-1945): Der Erfinder der modernen Laparoskopie.

On 23 September 1901, Georg Kelling (1866-1945) from Dresden performed a celioscopy with a Nitze cystoscope on a dog in Hamburg. This was the beginning of the era of laparoscopy.His doctoral thesis already reflected his early interest in the anatomy and physiology of the gastrointestinal tract. This experience, together with his knowledge on air insufflation of the abdomen, enabled him to be the first to develop the procedure he named "celioscopy." During this pioneer time of laparoscopy, he developed various basic principles that are still valid today and demonstrated astonishingly visionary skills. Although his pioneering achievements have hardly been acknowledged to this day, modern laparoscopy has confirmed Kelling's visions and scientific work in almost all aspects. His name and achievements have most definitely earned a place in the history of endoscopy.

Persistence, recurrence, and progression rates of superficial bladder tumours after resection using the differentiated technique.

OBJECTIVE: To investigate whether the differentiated resection technique for excising superficial bladder cancer leads to higher recurrence and progression rates as compared with regular resection. SUBJECTS AND METHODS: We evaluated 163 patients, 66 undergoing a differentiated and 97 a regular resection. All patients underwent a routine second resection within 6-10 weeks. Recurrence and progression rates as well as tumour persistence on second resection were analyzed. RESULTS: Patients with differentiated resections of bladder tumours did not have higher tumour recurrence and progression rates. Also, these patients had a significantly higher percentage of tumour-free second resections (p = 0.03). CONCLUSION: The differentiated resection technique for excising superficial bladder cancer has no negative influence on recurrence and progression rates, but it leads to a reduced tumour persistence.

Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel openers as a possible medical treatment of the overactive bladder and urge incontinence.

Urinary incontinence affects millions of people worldwide and also represents a social problem. People of all ages suffer from urinary incontinence. The disease is found in about 30% of women aged 30 to 60 years. There are different types of incontinence. Urge incontinence is the most often pharmacologically treated type. The mainly used substances belong to the class of antimuscarinic drugs. Their use is limited by several side effects. Furthermore, in some patients anticholinergic medication is ineffective and antimuscarinics used as single medication do not lead to a sufficient therapeutic effect. Other possible pharmacological substances for treatment of overactive bladder (detrusor instability) associated with urge and urge incontinence are the selective beta-adrenoceptor-agonists which are mainly responsible for the adrenergic mediated relaxation. It depends on the species, which beta-adrenoceptor-subtype (the beta2- and/or beta3-adrenoceptor) mainly mediates the relaxation. Non selective beta-adrenoceptor-agonists exhibit serious cardiovascular side effects like tachycardia or decrease of blood pressure by stimulating beta1- and beta2-adrenoceptors. These side effects should be decreased when using selective agonists. Additionally, substances whose targets are membrane channels of muscle cells could be interesting for treatment of overactive bladder. This group includes L-type calcium antagonists and potassium channel openers of ATP-sensitive potassium channels or BK channels. Especially the local use of the pharmacologically very potent calcium antagonists could be an interesting therapeutic approach, since systemic cardiovascular side effects were avoided. After chronic oral treatment with different calcium antagonists effects on the detrusor muscle were reduced or could not be detected, possibly due to an upregulation of 1,4-dihydropyridine-sensitive potassium channels. A very interesting approach is the use of potassium channel openers said to be selective for the urinary bladder. If there is a selectivity for the detrusor muscle, cardiovascular side effects were reduced. Possibly, the local use is a useful application form. Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel openers are pharmacological approaches, which are not yet available for clinical use.

Expression of transketolase TKTL1 predicts colon and urothelial cancer patient survival: Warburg effect reinterpreted.

Tumours ferment glucose to lactate even in the presence of oxygen (aerobic glycolysis; Warburg effect). The pentose phosphate pathway (PPP) allows glucose conversion to ribose for nucleic acid synthesis and glucose degradation to lactate. The nonoxidative part of the PPP is controlled by transketolase enzyme reactions. We have detected upregulation of a mutated transketolase transcript (TKTL1) in human malignancies, whereas transketolase (TKT) and transketolase-like-2 (TKTL2) transcripts were not upregulated. Strong TKTL1 protein expression was correlated to invasive colon and urothelial tumours and to poor patients outcome. TKTL1 encodes a transketolase with unusual enzymatic properties, which are likely to be caused by the internal deletion of conserved residues. We propose that TKTL1 upregulation in tumours leads to enhanced, oxygen-independent glucose usage and a lactate-based matrix degradation. As inhibition of transketolase enzyme reactions suppresses tumour growth and metastasis, TKTL1 could be the relevant target for novel anti-transketolase cancer therapies. We suggest an individualised cancer therapy based on the determination of metabolic changes in tumours that might enable the targeted inhibition of invasion and metastasis.

Protein profiling of bladder cancer using the 2D-PAGE and SELDI-TOF-MS technique.

Protein profiling is a promising tool for tumor characterization and the detection of tumor markers in bladder cancer. Techniques for 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and surface-enhanced laser desorption/ionization with time-of-flight mass spectrometry (SELDI-TOF-MS) have improved; both were evaluated using bladder tumor tissue. Normal urothelium and pTa G2, pT1 G3, and >or=pT3 G3 tissues were obtained from the operating room and, after macrodissection, subjected to 2D-PAGE and to SELDI-TOF-MS ProteinChip. 2D-PAGE gels expressed significantly different protein patterns for pTa G2 and pT3 G3 tumors. pT1 G3 tumors showed expression profiles similar to those of the invasive tumors, with upregulation of galectin 3, gelsolin, villin 2, moesin, and annexin 6. Similarly, distinct protein peaks were detected for superficial and muscle-invasive urothelial cancers by SELDI-TOF-MS. Six of seven superficial pTa G2 tumors showed an intense peak at 6.7 and 10.1 kD, while invasive carcinomas showed an intense peak near 9.5 kD. No disturbing influence of surrounding tissue on the results was detected. It was shown that both techniques (2D-PAGE and ProteinChip) work well, and especially ProteinChip analysis seems promising for clinical application.

[Wolfgang Amadeus Mozart. A urological pathography]. / Wolfgang Amadeus Mozart. Eine urologische Pathographie.

The death of Wolfgang Amadeus Mozart was mysterious from the very first day, and cause of wildest speculation and adventurous assertions. Over the last 100 years, medical science has investigated the physical sufferings and the mysterious death of Mozart with increasing intensity. By means of letters from his father Leopold, his sister "Nannerl", himself and reports from his physicians and contemporaries, we would like to create a medical pathography. The rumour that Mozart was poisoned appeared soon after his early death at the age of 35 on December 5th 1791, and was kept up persistently. Accused were the physician van Swieten, Mozart's freemason's loge and the royal band master Salieri. Mozart, however, died due to chronic kidney disease and ultimately due to uraemia. Once the renal damage has reached a certain point, a minimum of additional stress leads to decompensation. This catastrophe occurs typically within the fourth decade of life. When listening to Mozart's music, we should remember that this apparently happy person was actually a premature adult robbed of his childhood, whose short life was an endless chain of indisposition, over fatigue, misery, concern and illness.

[Foreign body in the urinary bladder after vascular surgery]. / Ein Corpus alienum in der Harnblase nach gefässchirurgischem Eingriff.

INTRODUCTION: We are presenting a rare complication after femorofemoral bypass surgery. CASE REPORT: In a 61-year-old male patient, a femorofemoral crossover bypass graft was inadvertently placed through the urinary bladder. Postoperatively, the patient developed macrohematuria, which cleared spontaneously. The diagnosis of an intravesical graft was made 3 months after surgery by cystoscopy performed because of dysuria. The patient underwent open bladder surgery 7 months later as he refused earlier intervention. The misplaced graft, which was not infected and showed good function and perfusion, was extravesically relocated. At a 16-month follow-up examination, the patient is free of urological symptoms and the bypass functions well. CONCLUSIONS: In case of dysuria or macrohematuria after vascular surgery in the vicinity of the urinary bladder, a misplaced bypass should be excluded.

[Current diagnostics and therapy of the overactive bladder and urge incontinence]. / Aktuelle Diagnostik und Therapie bei Harnblasenhyperaktivität und Dranginkontinenz.

Urinary incontinence affects millions of people worldwide and also represents a social problem. Costs of urinary incontinence and overactive bladder are very high. Urge incontinence is the involuntary loss of urine associated with a strong desire or urge to urinate. There are two types of urge incontinence: One is associated with involuntary detrusor contractions leading to a loss of urine, the other is characterized by a hypersensitive bladder in which micturition reflexes are induced due to an increased afferent activity. It is important to distinguish between an idiopathic type of urge incontinence and a symptomatic type possibly caused by infections, tumours, bladder stones or foreign bodies. Diagnostics is based on a careful medical history, clinical examination and urodynamic evaluation. The use of a voiding diary is necessary. Current agents for drug therapy rely upon their anticholinergic properties. Their use is limited by side effects such as blurred vision, dizziness, constipation and dryness of the mouth. Additionally, patients refractory to anticholinergic medication can be treated by endoscopic direct injection of botulinum toxin into the detrusor muscle. These patients can also be treated by intravesical application of vanilloid derivatives in the bladder leading to a desensitization of bladder sensory fibers. In some cases of refractory urge incontinence, electrical neuromodulation is effective. Other pharmacological approaches could be selective b-adrenoceptor agonists, calcium antagonists and potassium channel openers, but these substances are not yet available for clinical use.

Diverticular carcinoma of the urinary bladder: diagnosis and treatment problems. A case report.

OBJECTIVES: To report a case of a primary carcinoma arising in a vesical diverticulum. CLINICAL PRESENTATION AND INTERVENTION: A 59-year-old male patient presented with painless macrohematuria. A primary carcinoma arising in a vesical diverticulum was detected with cystoscopy and confirmed with rectal endosonography and computer tomography. and radical cystoprostatovesiculectomy with ileal conduit was performed. Chemotherapy with cisplatin and methotrexate followed. The patient died of an acute cardiac event in the 4th postoperative month. CONCLUSION: This report illustrates that in a case of a closed opening of a bladder diverticulum, rectal endosonography and computer tomography do provide additional support for making a diagnosis of a hidden tumor in the diverticulum.

[Early instillation in superficial bladder carcinoma. Current status]. / Die Frühinstillation des Harnblasenkarzinoms. Eine Standortbestimmung.

The high recurrence rate in superficial bladder cancer (>70%) is caused by the adhesion of free floating tumor cells during transurethral treatment, by incomplete resections, and by overlooked and new tumors. Frequent follow-ups and reoperations are necessary. A single immediate instillation after TUR shows positive effects in reducing recurrence rates and is therefore recommended in the European Guidelines from 2001. The amount, concentration, instillation time, and substances have not yet been standardized. By analyzing the literature we found many different techniques of early instillation therapy. Different substances, concentrations, varying instillation times, and application times make a comparison of these studies very difficult. Further studies are needed to standardize early postoperative instillation therapy.

In vitro transfection of human bladder cancer cells by acoustic energy.

BACKGROUND: The objective of this study was to examine and quantify the shock-wave-induced transfection of human bladder carcinoma cells. MATERIALS AND METHODS: Cell suspensions were transfected with different concentrations of the pEGFP-N1 plasmid. Shock-waves were applied in a degassed water bath with different numbers of impulses at different energy levels. Additionally, the effects of different DNA concentrations, frequencies and the absence/presence of a liquid air border were examined. RESULTS: After shock-wave application, the transfection rate increased up to a maximum of 27.10% after 1000 impulses at an energy level of 0.5 mJ/mm2. In comparison negative control groups were transfected significantly below 1%. An increase in acoustic power and frequency and of DNA concentration and the presence of a liquid-air border resulted in an increasing transfection rate. CONCLUSION: The results demonstrate that naked plasmid DNA can easily and effectively be delivered to malignant urothelial cells in vitro upon exposure to lithotripter-generated shock-waves.

[Surgery of metastases in renal cell carcinoma]. / Metastasenchirurgie beim Nierenzellkarzinom.

Renal cell carcinomas (RCC) are endowed with impressive metastatic potential. Patients with RCC who present with apparently solitary metastatic lesions represent a small cohort. Due to the different long-term results achieved with surgical resection of metastatic RCC lesions, a generally accepted judgement about this treatment modality is not possible. Several studies suggest that aggressive surgical management can provide an effective treatment, especially in patients with solitary pulmonary metastases. Most noteworthy is the fact that because of the organ distribution of RCC metastases, surgical therapy is dominated by general and thoracic surgeons, neurosurgeons, and orthopaedic surgeons. Therefore, an interdisciplinary approach is one of the most important key points for a successful outcome in these patients.