U. Steiner

Quantitative Detection of Human Complement Factor H-Related Protein in Transitional Cell Carcinoma of the Urinary Bladder

Objective: The purpose of this study was to assess a new quantitative urinary tumor marker for transitional cell carcinoma of the urinary bladder (TCC), human complement factor H-related protein (hCFHrp, BTA TRAKTM). Methods: Urine samples of 298 individuals (76 healthy volunteers, 118 patients with benign urologic disorders, 104 patients with histologically proven bladder cancer) were examined for the presence of hCFHrp. Samples of all patients were obtained prior to therapy. Results: In comparison to healthy volunteers, patients with TCC had significantly higher urinary levels of hCFHrp (117.60 vs. 2.05 U/ml; p < 0.001). HCFHrp levels were positively correlated with tumor grade and stage. Patients with invasive TCC had significantly higher levels of hCFHrp than patients with superficial TCC (p = 0.001). Marker levels in superficial bladder cancer at high risk of tumor progression (pT1G3) were significantly higher as compared to low and intermediate grade superficial cancers. Elevated levels of hCFHrp were also found in patients with benign urologic disorders (median: 72.65 vs. 117.60 U/ml in cancer patients). Using a cutoff of 17.1 U/ml, hCFHrp had a sensitivity of 72.1% and, due to a high rate of false-positive determinations in patients with benign urologic disorders, a total specificity of 50.5%. Conclusions: HCFHrp (BTA TRAKTM) is a sensitive test for detection of bladder cancer and for identification of patients at high risk. Due to a high rate of false-positive results in patients with benign urologic diseases, the test should not be used in an unselected population.

Expression of CD44V2 in transitional cell carcinoma of the urinary bladder and in urine.

CD44 is the principal cell surface receptor for hyaluronate. Variant forms of the receptor, produced by alternative splicing, have been found to be associated with tumor progression in a variety of cancers. Based on investigations at the RNA level, it has recently been proposed that expression of CD44 variant V2 was present in urothelial cancer but not in normal urothelium. Since a distinctive marker for urothelial cancer would be extremely useful, frozen sections of normal urothelium and urothelial cancer were examined for expression of standard CD44 and CD44V2. Frozen sections of specimens of 35 patients with transitional cell carcinoma of the bladder, 16 specimens of normal bladder and 5 ureters were examined. Immunohistochemical staining was performed using a polyclonal antibody to CD44V2 (PAB CD44V2), a monoclonal antibody to CD44V2 (MAB CD44V2) and a monoclonal antibody to CD44S (MAB CD44S). CD44V2 and CD44S were also measured in lysates of urine sediments from 21 patients by enzyme-linked immunoabsorbent assay (ELISA). All investigated transitional cell carcinomas expressed CD44V2. There was no differentiation between invasive and noninvasive carcinoma. CD44V2 was also expressed in normal urothelium. Standard CD44 was expressed by the transitional cell carcinoma, normal urothelium, musculature and interstitial tissue. The amount of CD44V2 and CD44S in lysates of urine sediments is not correlated to diagnosis. In contrast to investigations at the RNA level, CD44V2 on the protein level seems not to be a distinctive marker for urothelial cancer. Therefore, CD44V2 will not be a useful diagnostic marker for detection of transitional cell carcinoma.

Transvaginal Bone Anchors in Female Stress Urinary Incontinence: Poor Results

Objective: This study evaluates the results of a minimally invasive technique for correcting female stress urinary incontinence by transvaginal implantation of pubic bone anchors. Patients and Methods: Female stress urinary incontinence was treated by fixing a gelatin-coated Dacron sling between two miniature titanium anchors with Prolene sutures. Results: A total of 26 patients (median age 57.2 years) underwent the sling procedure. The follow-up examination was performed after 11.4 months on average. Stress incontinence showed a median improvement from grade 2 to grade 0.5 (p = 0.01), although only 16 of the 26 patients were completely continent. Urethral pressure and functional length were not significantly influenced. Impaired vaginal wound healing was seen in 14 of the 26 patients (53.8%), and 13 of them underwent revision. All patients affected (15/26, 57.7%) as well as 1 with uneventful healing showed sensory urge symptoms or detrusor instability (7/26, 26.9%). The correlation between impaired wound healing and detrusor instability was highly significant (p < 0.003). 17 of the 26 patients (65.3%) were dissatisfied or very dissatisfied with the intervention. The unfavorable results did not significantly correlate with the patients’ age, the number of previous operations, or the surgeon’s skill. Conclusion: In view of the poor vaginal wound healing and the resultant irritative symptoms, transvaginal bone anchoring with fixation of a Dacron sling must be regarded as an unsuitable technique.

Strahlentherapie nach radikaler Prostatektomie

ZusammenfassungHintergrundIn den letzten Jahren hat die Radiotherapie nach radikaler Prostatektomie bei organüberschreitenden Tumoren mit oder ohne positiven Schnittrand sowohl als adjuvante als auch als Therapie bei PSA-Anstieg unter der Vorstellung eines Lokalrezidivs bzw. eines lokalen Tumorrestes bei einem großen Anteil dieser Patienten zunehmend an Bedeutung gewonnen. Hintergrund hierfür ist die durch den Einsatz des PSA sich durchsetzende Erkenntnis, daß Patienten mit histopathologisch gesicherten pT3/4-Tumoren oder mit Befall der Lymphknoten durch eine alleinige operative oder eine alleinige strahlentherapeutische Therapie bereits nach drei bis fünf Jahren in bis zu 60% systemisch und/oder lokal progredient sind.ErgebnisseEine Vielzahl von allerdings ausschließlich retrospektiven Untersuchungen belegt eine signifikant erhöhte lokale Tumorkontrolle durch die Radiotherapie nach radikaler Prostatektomie. Das gilt sowohl für die adjuvante Therapie bei PSA im „Nullbereich” und bei PSA-Anstieg aus dem „Nullbereich,” wobei berücksichtigt werden muß, daß auch Patienten behandelt werden, bei denen kein lokaler Tumor vorliegt, und dies gilt auch bei histologisch gesichertem Lokalrezidiv. Mehrere Studien zeigen eine signifikante Verlängerung des „freedom from treatment failure”, das heißt des lokalen und systemischen Progresses. Eine Verlängerung des Gesamtüberlebens wurde jedoch bisher nicht nachgewiesen. Bei Anstieg des PSA aus dem „Nullbereich” nach radikaler Prostatektomie oder postoperativ erhöhtem PSA bestehen Hinweise, daß bei Werten oberhalb 2,5 bis 4 ng/ml bereits eine systemische Metastasierung besteht und die Radiotherapie keine kurative Intention mehr besitzt.SchlußfolgerungenDurch die lokale adjuvante Radiotherapie nach radikaler Prostatektomie wird sowohl die lokale Kontrolle als auch das „freedom from treatment failure” bei organüberschreitendem Prostatakarzinom mit positivem Schnittrand und wahrscheinlich auch negativem Schnittrand erhöht bzw. verlängert. Eine Verlängerung des Gesamtüberlebens wurde bisher nich bewiesen. Insgesamt drei prospektiv randomisierte Studien werden derzeit durchgeführt. Zur Frage der Strahlentherapie in Verbindung mit einer gleichzeitigen oder auch neoadjuvanten systemischen hormonellen Therapie liegen nur sehr spärliche, allerdings interessante Daten vor.AbstractBackgroundRadiation therapy following radical prostatectomy in locally progressed prostate carcinoma has become increasingly important in the last few years as both adjuvant therapy in patients with pT3-tumors with or without positive margins and treatment for a PSA increase in local recurrence of disease. The background for this is the knowledge gained by using PSA that up to 60% of the patients with histopathologically confirmed pT3/4 tumors or involvement of the lymph nodes are systemically and/or locally progressive after 3 to 5 years if only surgical or radiation therapy was performed.ResultsA number of studies, albeit exclusively retrospective, substantiated a significantly high local tumor control by radiotherapy after radical prostatectomy. This holds true for adjuvant therapy with a PSA in the “zero range” as well as with a PSA increase from the “zero range”, whereby it must be taken into consideration that a certain percentage of treated patients with a PSA in the “zero-range” with or without positive margins actually do not need further therapy. Two retrospective studies demonstrated a significant better lengthening of “freedom from treatment failure” that is local and systemic progression of disease. Lengthening the survival time has, however, not yet been proven. With an increase in the PSA from the “zero range” after radical prostatectomy, there are indications that systemic metastatic spread already occurs with values higher than 2.5 to 4 ng/ml and the radiotherapy no longer has any curative intention.conclusionsAdjuvant RT following radical prostatectomy gives better local control rates and probably better rates of “freedom from treatment failure” in patients with locally advanced prostate cancer with positive margins and probably in patients with negative margins. However, in retrospective studies no advantage in overall survival was shown.

The Value of PSA Measurements at 30 Gy, 50 Gy and 60 Gy for Dose Limitation in Patients with Radiotherapy for PSA Increase after Radical Prostatectomy

Background: Radiation therapy is a treatment option for patients with rising PSA after radical prostatectomy without histological evidence of local relapse and no signs of distant metastases. Prior to radiotherapy there is no certainty whether a patient is going to respond to the treatment or not. When total doses of more than 60 Gy are given there is an exponential rise in treatment-related late-toxicity. Therefore those patients in whom radiotherapy later appears to be ineffective may benefit from a dose restriction to 50–60 Gy. The aim of this study was to examine the prognostic value of PSA levels evaluated during radiotherapy. Patients and Methods: 41 patients with rising PSA level following prostatectomy received radiotherapy to the prostatic bed and were treated up to a median dose of 66.6 Gy. We evaluated serum PSA levels during radiotherapy at 30 Gy, 50 Gy and 60 Gy and compared them to the pre-radiotherapy PSA level and the outcome of radiotherapy. Results: After radiotherapy, 31 patients (76%) had either undetectable (n=15), or decreasing but still detectable PSA levels (n=16) and ten patients (24%) had rising PSA levels and did not respond. PSA evaluation at 30 Gy showed that 26% (8/31) of those patients who would respond to radiotherapy still had a rising PSA when compared to pretreatment PSA. At 50 Gy and 60 Gy 93% (27/29) of these patients had decreasing PSA levels. In contrast, 75% (6/8) and 88% (7/8) of those patients in whom radiotherapy was not effective had rising PSA levels at 50 Gy and 60 Gy (p<0.05). Conclusions: PSA measurements at 30 Gy, 50 Gy and 60 Gy for radiotherapy of PSA increase following radical prostatectomy without histologically proven local recurrence gives valuable information about the later tumor response. Therefore it possibly gives the opoprtunity to finish radiotherapy between 50 and 60 Gy, as almost all patients with continued PSA increase at 60 Gy do not stand to profit from radiotherapy. In these patients dose limitation would significantly decrease the risk of late side effects, especially for the bladder and the rectum. PSA evaluations at 30 Gy and 50 Gy or 60 Gy are recommendable.Hintergrund: Die Strahlentherapie ist eine Therapieoption für Patienten mit PSA-Anstieg nach radikaler Prostatektomie ohne histologische Sicherung eines Lokalrezidivs und ohne Zeichen einer Fernmetastasierung. Vor der Strahlentherapie gibt es keine Gewissheit, ob ein Patient auf die Therapie ansprechen wird oder nicht. Bei Gesamtdosen über 60 Gy kommt es zu einem exponentiellen Anstieg therapiebedinger Spätfolgen. Dehsalb könnten Patienten, bei denen sich die Strahlentherapie im Verlauf als ineffektiv erweist, von einer Dosisbegrenzung auf 50–60 Gy profitieren. Das Ziel dieser Studie war, den prognostischen Wert von PSA-Werten während der Strahlentherapie zu untersuchen. Patienten und Methoden: 41 Patienten mit steigenden PSA-Werten nach radikaler Prostatektomie erhielten eine Strahlentherapie im Bereich des Prostatabettes bis zu einer medianen Dosis von 66,6 Gy. Es wurden die Serum-PSA-Werte bei 30 Gy, 50 Gy und 60 Gy bestimmt und mit dem prätherapeutischen Wert sowie dem Behandlungsergebnis verglichen. Ergebnisse: Nach der Strahlentherapie hatten 31 Patienten (76%) entweder nicht messbare (n=15) oder fallende, aber noch messbare PSA-Werte (n=16), während zehn Patienten (24%) steigende PSA-Werte hatten und nicht auf die Therapie ansprachen. Die PSA-Bestimmung bei 30 Gy zeigte bei 26% (8/31) der Patienten, die auf die Strahlentherapie ansprachen, noch steigende PSA-Werte (verglichen mit dem prätherapeutischen Wert). Bei 50 Gy und 60 Gy hatten 93% (27/29) dieser Patienten fallende PSA-Werte. Im Gegensatz dazu hatten 75% (6/8) und 88% (7/8) der Patienten, die nicht auf die Strahlentherapie ansprachen, steigende PSA-Werte bei 50 Gy und 60 Gy (p<0,05). Schlussfolgerungen: PSA-Bestimmungen bei 30 Gy, 50 Gy und 60 Gy während der Strahlentherapie bei PSA-Anstieg nach radikaler Prostatektomie ohne histologisch gesichertes Lokalrezidiv geben wertvolle Hinweise über das mögliche spätere Therapieansprechen. Somit besteht unter Umständen die Möglichkeit, die Strahlentherapie zwischen 50 Gy und 60 Gy zu beenden, da fast alle Patienten mit weiterem PSA-Anstieg bei 60 Gy letztlich nicht von der Strahlentherapie profitierten. Bei diesen Patienten würde eine Dosisbegrenzung das Risiko von Spätfolgen signifikant senken, insbesondere an Harnblase und Rektum. PSA-Bestimmungen bei 30 Gy und 50 Gy oder 60 Gy sind empfehlenswert.

Curriculum in Urology: Phimosis and Circumcision in Children

ly around the glans, but they are blocked in the midline on the ventrum by the incompletely developed urethra. This preputial fold rolls over the base of the glans and leaves a groove between the coronal sulcus and the primitive prepuce. At the same time, an ingrowth of epithelium with thick cells, known as glanular lamella, actively proliferates in the groove in order to form a sheet between the preputial fold and the glans. This active epithelial proliferation in the groove carries the ridge of the preputial fold distally with the help of the mesenchymal growth within the prepuce [1]. The preputial and urethral folds fuse on the ventrum of the glans as the frenulum. The urethra within the glans penis develops by canalization of the urethral plate and the urethral orifice reaches its final destination at the site of the former epithelial tag. Formation of the frenulum seems to be required for completion of glandular urethral development [2]. After the 4th month of gestation, the single epithelial The prepuce, also called the foreskin, is the double-faced covering of the glans of the flaccid penis. Its inner surface is mucosa and outer surface is penile skin. The junction of these two surfaces is known as the preputial ring. Disorders of the prepuce, such as balanitis and phimosis, receive only cursory attention even in urological textbooks and their exact etiopathogenesis still remains unclear. Knowing the development of the prepuce is important to better understand its disorders and surgery.

Side Effects of Chemotherapy for Advanced Urothelial Carcinoma with Etoposide and Ifosfamide

OBJECTIVES To date, chemotherapy for advanced urothelial carcinoma has been associated with only moderate therapeutic success and minimal extension of survival. This, coupled with the occurrence of serious side effects and the resulting reduced quality of life, underscores the need for new chemotherapeutic agents. A first study investigating combination therapy with etoposide and ifosfamide reported not only comparable therapeutic effectiveness but, due primarily to the elimination of the cisplatin component, a reduction in nephrotoxic side effects. In the present study, therefore, patients with advanced urothelial carcinoma and minor compromised renal function received combination chemotherapy with etoposide and ifosfamide. METHODS Fourteen patients with advanced urothelial carcinoma underwent chemotherapy with a combination of etoposide and ifosfamide. On days 1-5, patients received 1,500 mg/m2 ifosfamide and 120 mg/m2 etoposide. The next corresponding cycle was started on day 22. RESULTS A number of serious side effects were observed. These consisted predominantly of high-grade myelosuppression requiring therapy, as well as disturbances in the central nervous system and impairment of renal function. Due to severe side effects, chemotherapy had to be prematurely terminated in 8 of 14 patients (57%). The efficacy of therapy, however, was observed in patients completing the treatment regimen. CONCLUSIONS The new combined chemotherapy with etoposide and ifosfamide shows efficacy in the treatment of advanced urothelial carcinoma. This, however, is overshadowed by the high rate of serious side effects leading to premature interruption of therapy.

Minimal-invasiver Knochenanker in der Therapie der weiblichen Stressinkontinenz Ein gutes Konzept?

ZusammenfassungDie vorliegende Untersuchung bewertet die Ergebnisse einer neuen minimal-invasiven Operationstechnik zur Korrektur der weiblichen Stressinkontinenz durch transvaginal in das Os pubis applizierte Knochenanker.Zwei Operationstechniken standen zur Verfügung: Die Zystourethropexie und die Implantation eines gelatinebeschichteten Polyethylenzügels zwischen 2 Ankern. Bei 4 von insgesamt 17 Patientinnen wurde eine Zystourethropexie durchgeführt, 13 erhielten eine Zügelplastik.Die Stressinkontinenz verbesserte sich im Mittel von Grad 2 auf 1,35 (p=0,01); 9 von 17 (53%) Patientinnen wiesen eine vaginale Heilungsstörung auf, 8 davon wurden revidiert. Es konnte keine signifikante Korrelation des ungünstigen Ergebnisses mit der Operationsmethode, dem Alter, der Zahl der Voroperationen oder dem Operateur errechnet werden.Aufgrund der überwiegend schlechten vaginalen Wundheilung und der damit häufig verbundenen irritativen Symptomatik muss die Technik der transvaginalen Knochenankerapplikation sowohl mit Zystourethropexie als auch mit einem Polyethylenzügel als ungeeignet bewertet werden.AbstractTransvaginal pubic bone anchoring represents a minimally invasive technique for cystourethropexy or urethral sling suspension. This study assesses the results of this procedure.Cystourethropexy was performed in 4 and a sling procedure in 13 of 17 patients. The stress incontinence showed a median improvement from grade 2 to 1.35 (p=0.01). Nine patients had impaired vaginal wound healing with urge symptoms. Revision was necessary in eight of them. An unfavorable outcome could not be significantly correlated with the surgical technique, the surgeon, the patients age or the number of previous operations.The technique of minimally invasive bone anchoring must be regarded as unsuitable in view of the largely poor wound healing associated with irritation symptoms.

The lymph node positive prostate cancer.A case for radiotherapy

SummaryThe role of radiotherapy of the pelvic lymphatic pathways in patients with node positive prostate cancer remains uncertain. Interpretation of the few prospective studies (RTOG 75–06 and 77–06) is hampered by severe flaws in the study design. Extension of the radiation to the paraaortal region shows no advantage over radiation of the pelvic lymphatics alone and is not warranted. Data on longterm side-effects are only available from older studies with outdated radiation techniques. According to more recent studies short term side effects are considerably higher with radiation of the pelvic lymphatics when compared with radiation of the prostate alone. In summary radiation of the lymphatic pathways in lymph node positive prostate cancer cannot currently be considered as standard treatment and should be carried out within clinical studies.ZusammenfassungDer Stellenwert einer Bestrahlung der pelvinen Lymphabflußwege beim lymphknotenpositiven Prostatakarzinom ist unklar. Prospektive Studien zu speziellen Fragestellungen liegen nicht vor oder sind methodisch umstritten (RTOG 75–06 und 77–06). Bei T3/4-Karzinomen bringt die zusätzliche Bestrahlung der paraaortalen Lymphabflußwege gegenüber der alleinigen Bestrahlung der pelvinen Lymphknoten keine Verbesserung des Gesamtüberlebens bzw. des progressionsfreien oder tumorspezifischen Überlebens und ist obsolet. Daten zu Langzeit-Nebenwirkungen liegen nur aus Studien mit veralteter Bestrahlungstechnik vor. Akut-Nebenwirkungen sind in neueren Serien bei Bestrahlung der Lymphabflußwege deutlich höher als bei Bestrahlung der Prostata allein. Die Strahlentherapie der Lymphabflußwege beim lympknotenpositiven Prostatakarzinom ist keine Standardtherapie sondern eine Individualentscheidung und sollte im Rahmen von Studien (z. B. ARO 95–3) durchgeführt werden.

UROTHELIAL CARCINOMA IN A SUPRAPUBIC CYSTOSTOMY TRACT 27 YEARS AFTER TUBE REMOVAL

A 57-year-old man was hospitalized with a skin tumor on the lower abdominal wall. Medical history included urinary retention in 1971 due to a urethral stricture of unknown etiology. Treatment consisted of a suprapubic catheter for 4 weeks followed by internal urethrotomy and catheter removal. Following an episode of macrohemaruria in 1995, pTa G2 transitional cell carcinoma of the left side of the bladder was resected. The patient had undergone regular followup including cystoscopy initially every 3 months and then every 6 months. Cystoscopy revealed no abnormal findings. In 1998, a few weeks after an inflammatory reaction of the skin above the symphysis pubis at the previous site of the suprapubic cystostomy, a solid tumor was detected on the cutis and the patient was referred to us. The last cystoscopy had been performed 7 months earlier. The skin at the previous cystostomy puncture site was slightly red with no signs of inflammation. An approximately 2 cm. tumor was seen directly above this site (fig. 1). Biopsy was suspicious of urothelial carcinoma with squamous cell differentiation. Abdominal