Thomas A. Vögeli

Identifying superficial, muscle-invasive, and metastasizing transitional cell carcinoma of the bladder: Use of cDNA array analysis of gene expression profiles

Purpose: Expression profiling by DNA microarray technology permits the identification of genes underlying clinical heterogeneity of bladder cancer and which might contribute to disease progression, thereby improving assessment of treatment and prediction of patient outcome. Experimental Design: Invasive (20) and superficial (22) human bladder tumors from 34 patients with known outcome regarding disease recurrence and progression were analyzed by filter-based cDNA arrays (Atlas Human Cancer 1.2; BD Biosciences Clontech) containing 1185 genes. For 9 genes, array data were confirmed using real-time reverse transcription-PCR. Additionally, Atlas array data were validated using Affymetrix GeneChip oligonucleotide arrays with 22,283 human gene fragments and expressed sequence tags sequences in a subset of three superficial and six invasive bladder tumors. Results: A two-way clustering algorithm using different subsets of gene expression data, including a subset of 41 genes validated by the oligonucleotide array (Affymetrix), classified tumor samples according to clinical outcome as superficial, invasive, or metastasizing. Furthermore, (a) a clonal origin of superficial tumors, (b) highly similar gene expression patterns in different areas of invasive tumors, and (c) an invasive-like pattern was observed in bladder mucosas derived from patients with locally advanced disease. Several gene clusters that characterized invasive or superficial tumors were identified. In superficial bladder tumors, increased mRNA levels of genes encoding transcription factors, molecules involved in protein synthesis and metabolism, and some proteins involved into cell cycle progression and differentiation were observed, whereas transcripts for immune, extracellular matrix, adhesion, peritumoral stroma and muscle tissue components, proliferation, and cell cycle controllers were up-regulated in invasive tumors. Conclusions: Gene expression profiling of human bladder cancers provides insight into the biology of bladder cancer progression and identifies patients with distinct clinical phenotypes.

Clinical Outcome of Patients with Lymph Node Positive Prostate Cancer after Radical Prostatectomy versus Androgen Deprivation

OBJECTIVE(S) To compare the outcome of patients with stage D1 (TxN+M0) prostate cancer undergoing radical prostatectomy or androgen deprivation alone. PATIENTS AND METHODS Eighty-two patients treated for lymph node positive prostate cancer were retrospectively analyzed for time to progression, tumor-specific and overall survival. Furthermore, subsequent tumor and treatment related morbidity requiring intervention including frequency and duration of associated hospital stays was recorded. RESULTS The extent of lymph node metastasis was significantly lower in 50 patients undergoing radical prostatectomy (+/- early androgen deprivation) compared to 32 receiving androgen deprivation only. The treatment groups, however, did not differ with regard to other characteristics including age, comorbidity, stage, grade and preoperative PSA. Mean actuarial progression-free, and tumor-specific survival was significantly longer for the radical prostatectomy patients (36% and 47%, respectively at 10 years) compared to androgen deprivation (15% and 32%, respectively). The latter group required more secondary interventions resulting in more frequent and overall longer hospital stays. CONCLUSIONS Patients undergoing radical prostatectomy for stage D1 prostate cancer possibly benefit with regard to the necessity for secondary interventions and, at least for limited (solitary) nodal disease, in terms of progression-free and tumor-specific survival. However, the latter observation may be biased by a larger extent of lymph node metastasis in the androgen deprivation group.

Urological Treatment and Clinical Course of BK Polyomavirus-Associated Hemorrhagic Cystitis in Children after Bone Marrow Transplantation

Hemorrhagic cystitis (HC) is a major complication of bone marrow transplantation (BMT). We describe the clinical course and urological management of BK polyomavirus-associated HC in children after bone marrow transplantation. From 8/88 to 11/95, a total of 117 consecutive pediatric patients received BMT. Nine patients (7.7%) developed HC after transplantation. HC in all 9 patients was characterized by late onset (day +24 to +50 post-BMT), long duration (1–7 weeks) and the excretion of BK polyomavirus in the urine as confirmed by electron microscopy, DNA hybridization and PCR techniques. Six children developed mild HC (grade 1–2) and were treated successfully by hyperhydration. In 3 patients, severe HC (grade 3–4) over 6 weeks required surgical interventions. In these 3 patients, cystoscopy revealed circumscript papulous tumors as the source of hematuria. Severe and persistent hematuria required blood transfusions, insertation of large suprapubic catheters and permanent bladder irrigation because of recurrent blood clot retention. Attempts to stop the hematuria in 2 of these patients by coagulation and laser vaporization (Nd:YAG) failed to stop the bleeding. Differential diagnosis of hematuria after BMT includes urinary tract infection, cyclophosphamide-induced chemical cystitis and bleeding due to BMT-induced thrombocytopenia. With the increasing number of BMTs in children, urologists may be confronted with BK polyomavirus-associated HC and must consider this in the differential diagnosis of hematuria after BMT.

Current laparoscopic practice patterns in urology: Results of a survey among urologists in Germany and Switzerland

OBJECTIVES A survey was performed to assess the current practice patterns in laparoscopy among urologists in Germany and Switzerland. METHODS Using the database directory of the German and Swiss Urological Association urological departments were identified. A detailed questionnaire was designed and sent by postal service. Responding questionnaires were analyzed. RESULTS The overall response rate was 64%. Fifty-four percent of respondents in Germany and 33% in Switzerland already perform laparoscopy; another 50% and 56% are planning to introduce laparoscopy. Thirty-six percent think that laparoscopy is economical and 77% await shortening of hospital stay. Major concerns are: Economical aspects, lengthy learning curve, investment, and lack of scientific data. The number of laparoscopic procedures during 12 months was registered for 19 indications. More than 40 procedures for one indication are performed by only 6% of the departments. CONCLUSIONS The survey reveals an increasing number of departments performing laparoscopy and broad acceptance of the technology but combined with some major concerns. Currently only a minority of the departments perform more than 40 procedures for one indication suggesting that at present laparoscopy is mainly a center-based technology.

Role of Interleukin‐6 in Stress Response in Normal and Tumorous Adrenal Cells and during Chronic Inflammation

Abstract: Interleukin‐6 (IL‐6) is the end‐product of a cytokine signaling cascade and is secreted by specialized immune cells during inflammation. It has a great influence on many functions, including differentiation, stimulation, and activation of immune cells, or other cells of neuroendocrine origin. Thus, IL‐6 serves as a key messenger in its communication with the neuroendocrine system, and serves as a potent activator of the hypothalamic‐pituitary‐adrenal axis at all levels. Changes in the levels of expression of this cytokine and its receptor have been observed during chronic inflammatory disease, and have been associated with tumorigenesis. Therefore, we studied the effect of IL‐6 on normal and adenomatous human adrenal cells in vitro. The expression of IL‐6 receptor mRNA was quantified within the same tissue. IL‐6 potently stimulated cortisol secretion from dispersed normal human adrenal cells. We found immunoreactivity for the IL‐6 receptor on cultured cells and paraffin‐embedded sections of adrenal tissues. Further, there was a more pronounced expression of IL‐6 mRNA in adrenal adenomas of patients with Cushings syndrome, compared to normal human adrenals. Despite this fact, the sensitivity of cells of adenomatous adrenal glands to IL‐6 was significantly decreased relative to cells from normal controls. These results were confirmed employing the permanent adrenocortical cancer cell line model NCI‐H295. We infer that the loss of responsivity of tumorous adrenal cells to IL‐6, and in part corticotropin, is an important step in the process of adrenal tumorigenesis by which regulation by differentiating proteins is bypassed.

[Prospective study of effectiveness. Reoperation (re-TUR) in superficial bladder carcinoma].

ZusammenfassungUm die Wertigkeit der systematischen Nachresektion zu untersuchen wurde eine prospektive Studie durchgeführt, um die Rate an residualem Tumor nach der Erstresektion zu erfassen. Nach dem Studienprotokoll wurden alle Patienten 6–8 Wochen nach der TUR einer Nachresektion (ReTUR) unterzogen. Residualer Tumor und seine Lokalisation sowie die Morbidität der ReTUR wurden dokumentiert.Bei insgesamt 192 im Studienzeitraum durchgeführten Resektionen fanden sich 124 histologisch gesicherte oberflächliche Tumoren. Von diesen wurden 83 gemäß dem Studienprotokoll nachreseziert. Bei 27% der pTa und 53% der pT1 Tumoren fand sich Tumorgewebe bei der Nachresektion. In 81% der Fälle fand sich der Tumor an früheren Resektionsstellen, bei 19% an anderer Lokalisation. In der multivariaten Analyse war nur die Differenzierung mit dem Nachweis von Tumor in der ReTUR korreliert.Die vorliegenden Daten dieser prospektiven Untersuchung sprechen für die Durchführung der systematischen ReTUR beim oberflächlichen Blasentumor.AbstractTo assess the rate of residual cancer after transurethral resection (TUR) of superficial bladder cancer, a prospective study was carried out. All patients with transitional cell cancer (TCC) stage pTa-pT1 underwent a repeat TUR (ReTUR) within 6–8 weeks. Sites and rates of tumors found during ReTUR were documented as well as the morbidity of the ReTUR.Of a total of 192 TUR, superficial TCC was found in 124 cases; 83 underwent ReTUR according to the study protocol. Residual tumor was detected in 27% of pTa and 53% of pT1 tumors. Worsening of grading or T stage was found in 8%. Of the tumors detected by ReTUR, 81% were localized at the site of the first TUR.In this prospective study, residual tumor formation was detected in a high percentage. Routine ReTUR is therefore recommended in superficial bladder cancer except solitary pTaGI lesions.To assess the rate of residual cancer after transurethral resection (TUR) of superficial bladder cancer, a prospective study was carried out. All patients with transitional cell cancer (TCC) stage pTa-pT1 underwent a repeat TUR (ReTUR) within 6-8 weeks. Sites and rates of tumors found during ReTUR were documented as well as the morbidity of the ReTUR. Of a total of 192 TUR, superficial TCC was found in 124 cases; 83 underwent ReTUR according to the study protocol. Residual tumor was detected in 27% of pTa and 53% of pT1 tumors. Worsening of grading or T stage was found in 8%. Of the tumors detected by ReTUR, 81% were localized at the site of the first TUR. In this prospective study, residual tumor formation was detected in a high percentage. Routine ReTUR is therefore recommended in superficial bladder cancer except solitary pTaGI lesions.

Ergebnisse der bundesweiten Datenerhebung über die urologische Laparoskopie

ZusammenfassungIm Rahmen einer Umfrage hat die Sektion Laparoskopie/Endoskopie der Fort- und Weiterbildungskommission der DGU den Stellenwert und die Einstellung zur Laparoskopie an urologischen Kliniken in Deutschland evaluiert. 183 von 300 angeschriebenen Kliniken haben den Fragebogen beantwortet (61%) und von diesen führen 54% Laparoskopien durch. Weitere 50% planen die Einführung der Technik. Vorbehalte bestehen im Hinblick auf die Wirtschaftlichkeit (70%), die Lernkurve (92%), die Investitionskosten (53%) und die unzureichende Datenlage (76%). Während die Nephrektomie aus benigner Indikation, der Kryptorchismus und die Varikozele von 66, 59 und 58 der 96 Kliniken laparoskopisch operiert werden, ist die radikale Prostatektomie und die Tumornephrektomie nur bei 32 und 34 der Kliniken etabliert. Über 40 dieser Eingriffe/Jahr werden nur von wenigen Zentren durchgeführt. Verglichen mit der Umfrage von 1995 hat die Akzeptanz des Verfahrens deutlich zugenommen (100 vs. 48%). Eine Operationsfrequenz von mehr als 40 Eingriffen/Jahr wird für größere Eingriffe nur von wenigen Kliniken angegeben.AbstractTo evaluate the current status of laparoscopy, the “Working Group Laparoscopy ”of the German Urological Association performed a questionnaire among urologists in Germany. Of 300 questionnaires 183 were returned and analyzed (61%): 54% of the departments already performed laparoscopy and another 50% are planning to introduce this technique. The major concerns are economical (70%), long learning curve (92%), investment (53%), and lack of scientific data (76%). Simple nephrectomy, cryptorchism, and varicoceles are treated by 66, 59, and 58 of the 96 departments laparoscopically (of 183 resp.). Laparoscopic surgery for radical prostatectomy and tumor nephrectomy is done by 32 and 34 of 96 departments. Only a minority of the centers performs more than 40 laparoscopies per year and indication. Compared to a survey conducted in 1995, the acceptance level of this technique has increased (100% vs 48%). Only a minority of the departments performs more than 40 laparoscopic interventions per year for one indication.

Ureterosigmoidostomy, Conduit and Continent Urinary Diversion

diversion. However, operative techniques are standardized today and the pouchrelated complication rates well known (2.8–4% early complications, 18–36.3% late complications). When a continent diversion cannot be performed, conduit diversion is required. The colonic conduit should be preferred in children and when life expectancy is long. With increasing life ex-pectancy of our patients, careful long-term follow-up (metabolic alterations, vitamins and secondary malignancies) after any type of urinary diversion become increasingly important and should be the subject of investigation.

Prospektive Studie zur WertigkeitNachresektion (ReTUR) beim oberflächlichen Blasenkarzinom

ZusammenfassungUm die Wertigkeit der systematischen Nachresektion zu untersuchen wurde eine prospektive Studie durchgeführt, um die Rate an residualem Tumor nach der Erstresektion zu erfassen. Nach dem Studienprotokoll wurden alle Patienten 6–8 Wochen nach der TUR einer Nachresektion (ReTUR) unterzogen. Residualer Tumor und seine Lokalisation sowie die Morbidität der ReTUR wurden dokumentiert.Bei insgesamt 192 im Studienzeitraum durchgeführten Resektionen fanden sich 124 histologisch gesicherte oberflächliche Tumoren. Von diesen wurden 83 gemäß dem Studienprotokoll nachreseziert. Bei 27% der pTa und 53% der pT1 Tumoren fand sich Tumorgewebe bei der Nachresektion. In 81% der Fälle fand sich der Tumor an früheren Resektionsstellen, bei 19% an anderer Lokalisation. In der multivariaten Analyse war nur die Differenzierung mit dem Nachweis von Tumor in der ReTUR korreliert.Die vorliegenden Daten dieser prospektiven Untersuchung sprechen für die Durchführung der systematischen ReTUR beim oberflächlichen Blasentumor.AbstractTo assess the rate of residual cancer after transurethral resection (TUR) of superficial bladder cancer, a prospective study was carried out. All patients with transitional cell cancer (TCC) stage pTa-pT1 underwent a repeat TUR (ReTUR) within 6–8 weeks. Sites and rates of tumors found during ReTUR were documented as well as the morbidity of the ReTUR.Of a total of 192 TUR, superficial TCC was found in 124 cases; 83 underwent ReTUR according to the study protocol. Residual tumor was detected in 27% of pTa and 53% of pT1 tumors. Worsening of grading or T stage was found in 8%. Of the tumors detected by ReTUR, 81% were localized at the site of the first TUR.In this prospective study, residual tumor formation was detected in a high percentage. Routine ReTUR is therefore recommended in superficial bladder cancer except solitary pTaGI lesions.To assess the rate of residual cancer after transurethral resection (TUR) of superficial bladder cancer, a prospective study was carried out. All patients with transitional cell cancer (TCC) stage pTa-pT1 underwent a repeat TUR (ReTUR) within 6-8 weeks. Sites and rates of tumors found during ReTUR were documented as well as the morbidity of the ReTUR. Of a total of 192 TUR, superficial TCC was found in 124 cases; 83 underwent ReTUR according to the study protocol. Residual tumor was detected in 27% of pTa and 53% of pT1 tumors. Worsening of grading or T stage was found in 8%. Of the tumors detected by ReTUR, 81% were localized at the site of the first TUR. In this prospective study, residual tumor formation was detected in a high percentage. Routine ReTUR is therefore recommended in superficial bladder cancer except solitary pTaGI lesions.

Prospektive Studie zur Wertigkeit Nachresektion (ReTUR) beim oberflächlichen Blasenkarzinom

ZusammenfassungUm die Wertigkeit der systematischen Nachresektion zu untersuchen wurde eine prospektive Studie durchgeführt, um die Rate an residualem Tumor nach der Erstresektion zu erfassen. Nach dem Studienprotokoll wurden alle Patienten 6–8 Wochen nach der TUR einer Nachresektion (ReTUR) unterzogen. Residualer Tumor und seine Lokalisation sowie die Morbidität der ReTUR wurden dokumentiert.Bei insgesamt 192 im Studienzeitraum durchgeführten Resektionen fanden sich 124 histologisch gesicherte oberflächliche Tumoren. Von diesen wurden 83 gemäß dem Studienprotokoll nachreseziert. Bei 27% der pTa und 53% der pT1 Tumoren fand sich Tumorgewebe bei der Nachresektion. In 81% der Fälle fand sich der Tumor an früheren Resektionsstellen, bei 19% an anderer Lokalisation. In der multivariaten Analyse war nur die Differenzierung mit dem Nachweis von Tumor in der ReTUR korreliert.Die vorliegenden Daten dieser prospektiven Untersuchung sprechen für die Durchführung der systematischen ReTUR beim oberflächlichen Blasentumor.AbstractTo assess the rate of residual cancer after transurethral resection (TUR) of superficial bladder cancer, a prospective study was carried out. All patients with transitional cell cancer (TCC) stage pTa-pT1 underwent a repeat TUR (ReTUR) within 6–8 weeks. Sites and rates of tumors found during ReTUR were documented as well as the morbidity of the ReTUR.Of a total of 192 TUR, superficial TCC was found in 124 cases; 83 underwent ReTUR according to the study protocol. Residual tumor was detected in 27% of pTa and 53% of pT1 tumors. Worsening of grading or T stage was found in 8%. Of the tumors detected by ReTUR, 81% were localized at the site of the first TUR.In this prospective study, residual tumor formation was detected in a high percentage. Routine ReTUR is therefore recommended in superficial bladder cancer except solitary pTaGI lesions.To assess the rate of residual cancer after transurethral resection (TUR) of superficial bladder cancer, a prospective study was carried out. All patients with transitional cell cancer (TCC) stage pTa-pT1 underwent a repeat TUR (ReTUR) within 6-8 weeks. Sites and rates of tumors found during ReTUR were documented as well as the morbidity of the ReTUR. Of a total of 192 TUR, superficial TCC was found in 124 cases; 83 underwent ReTUR according to the study protocol. Residual tumor was detected in 27% of pTa and 53% of pT1 tumors. Worsening of grading or T stage was found in 8%. Of the tumors detected by ReTUR, 81% were localized at the site of the first TUR. In this prospective study, residual tumor formation was detected in a high percentage. Routine ReTUR is therefore recommended in superficial bladder cancer except solitary pTaGI lesions.