[Lymphadenectomy for bladder cancer. Diagnostic and prognostic significance as well as therapeutic benefit]. / Lymphadenektomie beim Blasenkarzinom. Diagnostische und prognostische Bedeutung sowie therapeutischer Nutzen.

BACKGROUND: Pelvic lymphadenectomy for invasive bladder cancer is not a standardized procedure and its relevance for staging and prognoses is still under discussion. A number of retrospective studies have demonstrated a positive correlation between extent of lymphadenectomy and prognosis after radical cystectomy. MATERIALS AND METHODS: In a retrospective study, we correlated the extent of lymphadenectomy with survival after radical cystectomy. Thereafter, we conducted a prospective study to investigate the limits of pelvic lymphadenectomy and the pattern of lymphatic spread. RESULTS: Retrospectively, we found a significantly better survival for patients when 15 and more lymph nodes were removed. The individual surgeon was also evaluated as an important prognostic factor. CONCLUSIONS: Based on retrospective data, an extended and complete pelvic lymphadenectomy improves the prognosis. The cranial border should be at least at the level of the aortic bifurcation. A prospective randomized study will have to clarify the effect of lymphadenectomy on the prognosis of patients after radical cystectomy.

[Tyson's glands. On eponymic and discussion in urology and dermatology]. / Tyson-Drüsen. Zur Eponymik und Diskussion in Urologie und Dermatologie.

The use of eponyms in scientific terminology and particularly in medical terminology has a long tradition but discussion often arises especially since the involvement of the protagonists in the National Socialist regime which led to strong controversies (e. g. Clara, Stieve, Reiter, Wegener). They are a component of cultural specialist memories and contribute to the conciseness of the nomenclature. For the specialization of urology a total list of eponyms in general use or an analysis of the use of eponyms does not exist. The eponym Tyson's glands is a good example of the tradition of eponyms in urology and the discussion about the related anatomical facts.

p53 immunoreactivity in biopsy specimens of T1G3 transitional cell carcinoma of the bladder--a helpful parameter in guiding the decision for or against cystectomy?

The aim of this study was to determine whether p53 is helpful in making the decision to undergo cystectomy in T1, G3 transitional cell carcinoma (TCC) of the bladder, by prospectively comparing the p53 status of bladder biopsies with the histology and p53 status of the corresponding cystectomy specimens. From January 1996 to August 1997, 38 consecutive patients with T1G3 TCC at 6 different centres were enrolled into the study. Bladder biopsies and cystectomy specimens were examined with three different antibodies against p53. The p53 status of each bladder biopsy was compared with p53 status, tumour stage and grade of the cystectomy specimen. An independent evaluation of the histology and immunohistochemistry was carried out by two pathologists. 15 of 38 patients (39%) were found to have a higher tumour stage in the cystectomy specimen compared with the staging by transurethral resection of the bladder tumour (TUR-B). 3 patients did not show residual tumour in the cystectomy specimen. No differences in p53 positivity were noted between the different antibodies. 14 of 31 evaluable tumours (45%) were p53 positive at the time of the TUR-B. p53 staining of the TUR-B specimen did not correctly predict the residual tumour in the cystectomy specimen. We, therefore, concluded that compared with standard histopathology, the p53 status of the TUR-B specimen does not provide additional relevant information with regard to local tumour staging and, thus, is not helpful in making the decision for or against a cystectomy.

Lack of efficacy of recombinant human interleukin-6 in patients with advanced renal cell cancer: results of a phase II study.

The present phase II study was undertaken to assess antitumoral activity, safety and tolerability of recombinant human interleukin-6 (rh IL-6) in patients with advanced renal cell cancer. Rh IL-6 was administered as a daily subcutaneous injection at a fixed dose of 150 micrograms/day for a maximum of 42 consecutive days. 12 patients with metastatic renal cell cancer without previous immunotherapy were enrolled and were evaluated for response. No objective clinical responses were observed in the trial. Toxicity was moderate and reversible and mainly comprised fever, influenza-like symptoms, fatigue and moderate hepatotoxicity. Anaemia, leucocytosis, thrombocytosis and induction of an acute phase response were observed in most patients. In conclusion, prolonged subcutaneous administration of rh IL-6 on an outpatient basis is safe and feasible. However, rh IL-6 exhibited no antitumoral activity in patients with metastastic renal cell cancer. Profound regulatory effects on haematopoiesis and inflammatory response of rh IL-6 were observed.

Effects of moclobemide on sexual performance and nocturnal erections in psychogenic erectile dysfunction.

RATIONALE AND OBJECTIVES: We tested the hypothesis that the selective reversible MAO-A inhibitor moclobemide has a specific therapeutic effect on erectile dysfunction independent of its antidepressive properties. METHODS: In a double-blind placebo controlled study, 12 male outpatients suffering from psychogenic erectile dysfunction without any other psychiatric disorder were investigated. Based on comprehensive diagnosis before the beginning of the study, organic factors relevant for sexual function were excluded. The treatment period was 8 weeks. Half the patients received 450 mg moclobemide during the first week, and 600 mg afterwards; the others received placebo. Apart from assessment of erectile function by means of the Clinical Global Impression (CGI) scale, nocturnal erections were measured under polysomnographic control at baseline and at the end of the treatment period. RESULTS: The evaluation of the CGI scale revealed a clearly stronger improvement under moclobemide compared to placebo during the study period. The therapeutic efficacy found on the subjective level had no clear correlate on the neurophysiological level. No alterations of nocturnal erectile parameters were obvious under treatment, neither were clinically relevant alterations found regarding sleep EEG parameters. The medication was well tolerated without serious adverse events. CONCLUSIONS: The findings support the hypothesis that moclobemide has a specific effect on erectile dysfunction. Thus, patients suffering from psychogenic erectile dysfunction who are not depressed might benefit from moclobemide without relevant side effects.

The effects of phorbol esters on choline phospholipid hydrolysis in heart and brain.

The efflux of choline was determined in rat striatal slices, incubated chicken atria and perfused chicken hearts. 4 beta-Phorbol-12 beta,13 alpha-dibutyrate (PDB) and 4 beta-phorbol-12 beta-myristate, 13 alpha-acetate (PMA) were used to stimulate protein kinase C. The other phorbol esters, 4 beta-phorbol-13 alpha-acetate (PAc) and 4 alpha-phorbol-12 beta,13 alpha-didecanoate (4 alpha PDD), known to be inactive, were tested to evaluate the specificity of the responses. PDB markedly enhanced the efflux of choline in all of the three preparations. The PDB-evoked efflux of choline in incubated chicken atria was equal to the net production of choline and, therefore, was not caused by translocation of intracellular free choline. After inhibition of the cholinesterase activity, PDB linearly increased the efflux of choline in rat striatal slices, but failed to alter the spontaneous efflux of acetylcholine. Thus acetylcholine did not serve as the source of the PDB-evoked efflux of choline. PMA was as effective as PDB, whereas PAc and 4 alpha PDD failed to alter the choline efflux in the perfused heart. Both infusion of a Ca2(+)-free EGTA-containing Tyrode solution and mepacrine reduced the spontaneous efflux of choline by about 40% and blocked the PDB-evoked efflux of choline. In contrast, a Ca2(+)-free solution without EGTA failed to alter the spontaneous and the PDB-evoked choline efflux. It is concluded that phorbol esters stimulate the hydrolysis of choline-containing phospholipids in heart and brain via activation of protein kinase C.

Xenobiotic metabolizing enzyme activities in isolated and cryopreserved human liver parenchymal cells.

Liver parenchymal cells (hepatocytes) of human organ donors were isolated using a two-step collagenase perfusion technique. The average viability of the freshly isolated liver parenchymal cells, as judged by trypan blue exclusion, was 82% (SD = 7%; n = 6). The inter-individual differences in the determined enzyme activities were less than a factor of 7.5, despite the different sexes and ages of the donors. Freshly isolated parenchymal cells (PC) were cryopreserved using a computer-controlled freezing protocol. After thawing, cryopreserved cells had a mean viability of 57% (SD = 18%; n = 6). The activities of xenobiotic metabolizing enzymes in freshly isolated and cryopreserved cells were compared using PC from two donors. The enzyme activities of phenol sulfotransferase, 1-naphthol UDP-glucuronosyltransferase and microsomal epoxide hydrolase were well maintained after thawing (87-117% of activities in freshly isolated cells), whereas the activities of glutathione S-transferase, monitored with the broad spectrum substrate 1-chloro-2,4-dinitrobenzene, and the major broad spectrum cytosolic epoxide hydrolase were moderately but markedly reduced after cryopreservation (34-64% and 45-89% of levels in fresh cells, respectively). The decrease of both activities was dependent on the viability after thawing. When cryopreserved cells were purified by a Percoll centrifugation after thawing, the viability was increased from 62 to 92% for cells from one of the donors and from 88 to 98% for PC for the other donor. Subsequently the activity of glutathione S-transferase in Percoll-purified PC from the two donors was increased to 71 and 96% of levels in freshly isolated cells. It is concluded that the use of cryopreserved liver parenchymal cells of humans and other species represents a valuable tool in predicting which animal species best represents humans in hepatic metabolism and therefore should be the preferred species for investigations of metabolism and metabolism-dependent toxicities.

[3-dimensional reconstruction for planning surgical reconstruction of tumors in the single kidney]. / Dreidimensionale Rekonstruktion zur Operationsplanung bei Tumoren in Einzelnieren.

Organ-sparing renal surgery for renal cell carcinoma has greatly increased in importance over the last few years owing to the widespread application of ultrasound examination. When a normal contralateral kidney is present the indications for organ-sparing surgery are very strict. Our patient presented with a large tumour in a single kidney and, though fully informed about all the risks involved, insisted upon an organ-sparing operation. In planning and execution of the operation we were much assisted by the use of a three-dimensional reconstruction made from the CT scan carried out preoperatively, because this showed the exact position and size of the tumour. We report on the course of the patient's illness and present a simple three-dimensional reconstruction technique.

[Ambulatory vasectomy. Risks and complications]. / Die ambulante Vasektomie. Risiken und Komplikationen.

Vasectomy is the simplest and most effective method of permanent sterilization in men. In most cases, the surgical technique includes conventional vasoresection with incision of the scrotal skin or no-scalpel vasectomy as a minimally invasive method. The most important complications following surgery are haemorrhage and haematoma (1.2%), infection (3.5%), epididymitis/epididymo-orchitis (2.1%), sperm granuloma (2-70%), and chronic pain (3-8%). No long-term negative organic effects have been proven in clinical studies. The surgeon's experience and the technique applied are essential for the postoperative course, whereas performing vasectomy either on an in-patient or out-patient basis does not seem to have an influence. To evaluate the success of the vasectomy, follow-up spermiograms are obligatory. If immotile spermatozoa are present further follow-ups are necessary. Vasectomy needs to be reperformed if motile spermatozoa are detected. The chance of an unsuccessful vasectomy is below 1%. Unprotected intercourse must not be performed before two consecutive spermiograms show azoospermia.

[Ranking of pelvic lymphadenectomy in therapy and prognosis of carcinoma of the bladder]. / Stellenwert der pelvinen Lymphadenektomie für Therapie und Prognose des Harnblasenkarzinoms.

PURPOSE: Due to the absence of internationally recognised guidelines on the necessary extent of lymphatic node removal in carcinoma of the bladder, we are still not sure as to which procedure is most favourable to therapeutic success. Hence, we checked retrospectively on the influence exercised by radical surgery on prognosis. MATERIAL AND METHOD: 506 patients were analysed retrospectively after radical cystectomy and pelvic lymphadenectomy with regard to the influence exercised on prognosis by clinical and histopathological variables. RESULTS: Statistically significant influential factors in univariate analysis were in the retrospective examination: the pT category (p < 0.0001), lymphatic node status (p < 0.0001), grading (p = 0.0145), proof of uronephrosis (p = 0.0007), number of performed transurethral resections (p = 0.0043), surgeon (p = 0.0033) and number of resected lymph nodes (p = 0.0012). There was a significant difference between surgeons at a median number of 14.3 removed lymphatic nodes (range 1 - 46) in respect of radicality (p = 0.001) and prognosis (p < 0.0049). Independent influential factors in multivariate analysis were: pT category (p = 0.003), pN category (p < 0.001) and the number of surgically removed lymphatic nodes (p = 0.038). CONCLUSION: In our retrospectively examined group of patients extensive lymphadenectomy significantly improved the prognosis and was thus a potentially curative procedure. Basing on these results, prospective studies will have to clarify the level of the standard applicable to pelvic lymphadenectomy and also the advantages and prospects of radical surgery in respect of possible patient survival.

[The early development of brachytherapy of the prostate: a study on technique application in the development of urology]. / Zur frühen Entwicklung der Brachytherapie der Prostata : Eine Studie zur Technikanwendung in der Urologieentwicklung.

Within recent years brachytherapy of the prostate has become a treatment of choice. The treatment can be dated back up to the beginning of the twentieth century. It is interesting that the urological routes have never been explored directly by authors of articles and textbooks in the field of radiology and radiooncology.

Prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 immunoreactivity in pT1 G3 urothelial bladder carcinomas.

pT1 G3 bladder carcinomas are heterogeneous with respect to tumor recurrence and progression. Whereas some urologists treat these carcinomas by repeated transurethral resections often followed by intravesical chemotherapy or BCG instillation, others recommend cystectomy after tumor recurrence or early cystectomy after the initial diagnosis. Our goal was to determine the prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak, and Ki-67 immunoreactivity in these tumors. There were 30 patients with a new histopathological diagnosis of pT1 G3 urothelial carcinoma based on a transurethral resection specimen. Representative sections of these specimens were examined for the above markers. All patients were followed up regularly and were classified as being tumor free or having tumor recurrence or progression. The mean follow-up period was 43 months (range: 8-102 months). Twenty-five patients underwent radical cystectomy and 7 of these (28%) suffered from tumor progression and died of bladder cancer. In 5 patients, surgery was limited to a transurethral resection and 4 of these patients developed superficial tumor recurrence. There was a significant difference in tumor-free survival between patients with p53-immunoreactive (mean: 30 months) and p53-negative tumors (mean: 82 months; p = 0.0341). Bcl-2 positivity was also associated with decreased tumor-free survival (p = 0.043). The other markers had no significant prognostic impact. We conclude that p53 and Bcl-2 immunoreactivity labels the most aggressive pT1 G3 bladder carcinomas.

Vaginal reconstruction using the bladder and/or rectal walls in patients with radiation-induced fistulas.

OBJECTIVE: In irreparable or recurrent vesicovaginal fistulas and cloacal defects following high-dose irradiation therapy for gynecological malignancies, urinary diversion is the last resort to achieve a socially acceptable solution. In a select group of young and tumor-free patients, additional vaginal reconstruction may be indicated. Multiple operative procedures are available, but the results are often disappointing in the previously irradiated area. MATERIALS AND METHODS: In six such patients with large radiogenic vesicovaginal defects (n = 5) or a cloacal fistula (n = 1), a continent reservoir using the transverse colon with an umbilical stoma was performed. At the end of the operation, the bladder was incorporated into a neovagina by incising the urethra, anterior vaginal wall, and the posterior bladder wall with electrocautery from the urethral meatus to the dome of the fistula. RESULTS: No postoperative complications related to the vaginal reconstruction occurred. After a mean follow-up of 4.7 years, all patients had a capacious vagina and a wide introitus; the neovagina measured a mean of 18 cm in length. Five patients with a partner reported a normal sexual life. No dyspareunia or discomfort from bladder or urethral mucosa during intercourse was reported. CONCLUSIONS: Following continent urinary diversion due to irreparable vesicovaginal fistulas, a neovagina can be created by simple dissection of the posterior bladder and anterior vaginal wall. When a colostomy is present, the neovagina can additionally be augmented with a bowel flap of the Hartmann stump or by incising the rectovaginal septum. The technique affords good functional and cosmetic results.

Lymphadenectomy in patients with transitional cell carcinoma of the urinary bladder; significance for staging and prognosis.

OBJECTIVE: To determine the need to standardize the number and location of lymph nodes to be removed during radical cystectomy in patients with invasive bladder carcinoma. PATIENTS AND METHODS: The pelvic lymph nodes from 447 patients (mean age 62.8 years) who underwent radical cystectomy between 1986 and 1997 were evaluated. The number of lymph nodes was correlated with the depth of invasion of the primary tumour (pT), occurrence of nodal metastases, clinical outcome, the operating surgeons and the pathologists dissecting the nodes. RESULTS: The clinical follow-up was available for 302 patients (mean follow-up 38.7 months). The mean (range) number of lymph nodes removed was 14.7 (1-46). The number of lymph nodes removed varied significantly among different surgeons but not among pathologists. In pT3 and pT4 tumours, a more extended lymphadenectomy (>/= 16 lymph nodes) correlated with a higher percentage of patients with documented nodal metastases. There was a significant correlation between the number of lymph nodes removed and the tumour-free 5-year survival in patients with pT1, pT2 or pT3 tumours, and in patients with 1-5 positive lymph nodes (P < 0.01). CONCLUSION: Extensive lymphadenectomy significantly improves the prognosis of patients with invasive bladder cancer and represents a potentially curative procedure in patients with nodal metastases, including micrometastases that may escape detection during routine histopathological evaluation. The results indicate the need for a standardized lymph node dissection.

[Significance of pelvic lymphadenectomy for the prognosis after radical cystectomy]. / Die Bedeutung der pelvinen Lymphadenektomie für die Prognose nach radikaler Zystektomie.

OBJECTIVE: In contrast to other carcinomas such as breast or colon cancer, there are no guidelines regarding the number and location of lymph nodes to be removed during radical surgery in patients with invasive bladder carcinoma. The therapeutic effect of pelvic lymphadenectomy and its influence on tumour staging has not been documented yet. METHODS: Here we present an evaluation of pelvic lymph nodes from 484 patients who underwent radical cystectomy with curative intention between 1986 and 1999. The number of lymph nodes was correlated with the depth of invasion of the primary tumour, occurrence of nodal metastases, clinical outcome, the operating surgeon, and the pathologist. RESULTS: There were 484 patients with a mean age of 62.7 years. Clinical follow up was available from 321 patients with a mean follow up period of 35.9 months. The average number of lymph nodes removed was 14.3 (range: 1-46). The number of lymph nodes removed varied significantly between different surgeons and did not correlate with the pathologists. There was a significant correlation between the number of lymph nodes removed and the tumour-free survival in pT2 or pT3 tumours and in patients without lymph node metastases. Multivariate analysis revealed that pT-category (p < 0.01), pN-category (p < 0.01), and the total number of lymph nodes removed (p = 0.04) were the most important factors affecting survival. CONCLUSION: The more extensive lymphadenectomy significantly improved the prognosis of patients with invasive bladder cancer and therefore, represents a potentially curative procedure. The results indicate a need for a standardised lymph node dissection.

[Infarct of the lower renal artery segment: diagnosis with CT-angiography and 3-dimensional spatial representation]. / Infarkt des unteren Nierenarteriensegmentes: Diagnose mittels CT-Angiographie und dreidimensionaler Raumformatierung.

The case of a CT-angiographically diagnosed partial renal infarction is presented. The infarction was diagnosed during a postoperative CT-control of the arteries after implantation of an aorto-biliac dacron graft. Reformatting of the axial spiral scans data was elaborated with surface rendering, maximum intensity projection, and volume rendering for comparison. Each of the reformatting modalities was able to re-present the renal infarction, elaboration time is short and a clear presentation of the spatial relationship can be obtained.

Colon pouch (Mainz pouch III) for continent urinary diversion after pelvic irradiation.

OBJECTIVES: Urinary diversion after previous pelvic irradiation is challenging. The use of irradiated bowel in particular is associated with an increased rate of early and late complications. We therefore performed continent cutaneous urinary diversion using exclusively nonirradiated bowel segments in this group of patients. METHODS: A continent colon pouch for urinary diversion was performed in 44 female patients after pelvic irradiation. The indications were irreparable vesical fistula in 20, local recurrence of gynecologic tumors in 22, and radical cystectomy for bladder cancer in 2 patients. Depending on the length of the nonirradiated bowel segment, a transverse-ascending colon pouch (n = 8) or transverse-descending colon pouch (n = 36) was performed. The efferent segment was created from a tapered bowel segment embedded in the pouch wall. The ureters were implanted using a submucosal (n = 67) or subserosal (n = 17) extramural tunnel. RESULTS: No pouch-related complications were observed during the immediate postoperative period. In long-term follow-up (mean 52.2 months), upper urinary tract dilation was seen in five renal units. All five of these had been dilated preoperatively, and none required ureteral reimplantation. Incontinence occurred in 2 patients; both underwent reoperation with subsequent continence. Umbilical stoma stenosis was observed in 6 patients. CONCLUSIONS: The technique of the colon pouch for continent urinary diversion in previously irradiated patients is safe and has a low complication rate. The use of nonirradiated bowel segments should be the method of choice in this group of patients.

Prognostic significance of histopathological grading and immunoreactivity for p53 and p21/WAF1 in grade 2 pTa transitional cell carcinoma of the urinary bladder.

OBJECTIVE: At present, there are no predictors of tumour behaviour for grade (G) 2 pTa transitional cell carcinomas (TCC) of the bladder. Here we analyse the prognostic relevance of histopathological grading and the immunohistochemical detection of p53 and p21/WAF1. METHODS: 70 patients were newly diagnosed with G2 pTa TCC of the bladder based on transurethral resection specimens. Two pathologists, blinded with respect to the clinical outcome, confirmed the initial grade and subclassified the G2 lesions into G2a and G2b carcinomas based on the degree of nuclear atypia and the number of mitoses. Immunoreactivity for p53 and p21/WAF1 was evaluated semiquantitatively. RESULTS: There were 52 G2a and 18 G2b tumours, mean follow-up was 49.2 months. Of all patients, 31.4% remained tumour-free, 48.6% recurred with the same tumour grade and stage, and 20.0% showed tumour progression. Patients with G2a tumours developed tumour progression in 13% in contrast to 39% with G2b lesions (p = 0.037). Of 21 p53-positive tumours, 33% (7/21) developed progressive disease, whereas 14% (7/49) of p53-negative patients showed tumour progression (p = 0.102). Neither p21/WAF1 expression alone nor the combination of p53 and p21/WAF1 correlated with clinical outcome. CONCLUSION: The more detailed grading system but not p53 or p21/WAF1 immunohistochemistry was found to be an independent prognostic factor for tumour progression.

Three-dimensional reconstruction of anatomic structures using serial sectional images.

Precise three-dimensional modeling and visualization of human anatomy and pathology are important in medicine. Three-dimensional models have applications in the training of medical students and residents and aid physicians evaluate and determine appropriate clinical management of patients. Three-dimensional reconstructions of radiographic images have been available for some time now. However, electronic reconstruction of these images often requires the utilization of large computer systems or workstations and also requires highly trained and specialized technicians to perform the task. This paper presents a technique for precise three-dimensional reconstruction of the human anatomy and pathology using an 80486 IBM compatible personal computer and commercially available software. We reconstructed the images from computed tomography scans. Implementation of this technique does not require extensive training and shows good results after a short learning curve.