G. Zöller

Regression of human metastatic renal cell carcinoma after vaccination with tumor cell-dendritic cell hybrids

Reports of spontaneous regressions of metastases and the demonstration of tumor-reactive cytotoxic T lymphocytes indicate the importance of the hosts immune system in controlling the devastating course of metastatic renal cell carcinoma. Recent research indicates that immunization with hybrids of tumor and antigen presenting cells results in protective immunity and rejection of established tumors in various rodent models. Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion techniques, we generated hybrids of autologous tumor and allogeneic dendritic cells that presented antigens expressed by the tumor in concert with the co-stimulating capabilities of dendritic cells. After vaccination, and with a mean follow-up time of 13 months, four patients completely rejected all metastatic tumor lesions, one presented a ‘mixed response’, and two had a tumor mass reduction of greater 50%. We also demonstrate induction of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our data indicate that hybrid cell vaccination is a safe and effective therapy for renal cell carcinoma and may provide a broadly applicable strategy for other malignancies with unknown antigens.

Treatment of Iatrogenic Postoperative Ureteral Strictures with Acucise Endoureterotomy

OBJECTIVES To determine factors influencing the outcome of Acucise endoureterotomy in patients with iatrogenic postoperative ureteral strictures after different open surgical procedures. MATERIAL AND METHODS Acucise endoureterotomy was performed in 18 patients with ureteral strictures after pyeloplasty (n = 5), renal transplantation (n = 5), ureteroenteric anastomosis (n = 3), calicoureterostomy (n = 1), ureterocystoneostomy (n = 1), hysterectomy (n = 1), ureterorenoscopy (n = 1) and transurethral resection of the ureteral orifice (n = 1). Success was determined as relief of clinical symptoms, improvement of renal function or improvement of radiographic findings. RESULTS The overall success rate was 61% (mean follow-up: 21.5 months). Six out of 18 patients showed relevant side effects. Neither the localization of the stricture nor the duration of postoperative ureteral stenting but the length of the stricture had influence on the postoperative outcome. Decreased renal function to less than 25% of the total function was always associated with failure of the treatment. The time period between the ureteral injury and the appearance of the ureteral stricture had influence on the outcome of the treatment. CONCLUSIONS Acucise endoureterotomy is effective in the treatment of postoperative ureteral strictures, but only in selected cases. The selection criteria are the time period from the primary operation to the appearance of the stricture (>6 months), the length of the stricture (<1.5 cm) and the renal function (>25% of the total function). In other cases, open surgical treatment of the ureteral stricture may provide better results.

Histologic and molecular evidence of obstructive uropathy in rats with hereditary congenital hydronephrosis.

Abstract Partial obstruction of the upper urinary tract, a frequent challenge for the pediatric urologist, leads to renal damage, if deobstruction is delayed. Several but sometimes unsatisfactory animal models have been developed to study this phenomenon. Obstruction created by surgical manipulation lacks adequate correlation with a developing congenital obstruction. In some animals with congenital hydronephrosis, evidence of renal obstruction is absent. A study of the renal morphology of rats with hereditary unilateral hydronephrosis has exhibited clear evidence of renal obstruction distinguishable from renal dilatation. The renal mRNA expression of renin and transforming-growth factor- β1 (TGF-β1) was measured by a semiquantitative RT-PCR technique. In hydronephrotic kidneys, a marked loss of parenchyma, atrophy and dilation of tubuli and collecting ducts and interstitial fibrosis was observed. The mRNA expression of renin was increased significantly in comparison to controls, whereas the contralateral kidneys showed renin activity below control levels. TGF-β1 expression was markedly increased in hydronephrotic kidneys, whereas contralateral kidneys did not differ significantly from control values. These data suggest the presence of renal obstruction and not only renal dilatation in these rats with congenital hydronephrosis. This colony seems to be a representative animal model to study congenital renal obstruction even in the fetal period without the need of surgical manipulation.

IMPAIRED NEPHROGENESIS IN RATS WITH CONGENITAL OBSTRUCTIVE UROPATHY

PURPOSE Alterations caused by renal obstruction in developing kidneys are of particular interest in basic research of congenital obstructive uropathy. In rats nephrogenesis mainly occurs 7 to 10 days postnatally. Therefore, surgically induced neonatal ureteral obstruction in rats has been suggested to be analogous to congenital obstruction in the fetus. An attempt less prone to surgical artifacts and assessing even earlier developmental stages is to monitor the development of obstructed kidneys in rats with congenital obstructive uropathy. MATERIALS AND METHODS Rats from an inbred strain with congenital renal obstruction in 70% of their littermates were observed. Morphologically, significant hydronephrosis was not detected before day 5 post partum and progressed with age. Unilateral obstructed kidneys were compared with contralateral kidneys and kidneys from healthy control animals at ages of 1, 5, 10, 18 and 32 days. A total of 72 renal units were investigated. The renal messenger RNA expression of renin and transforming growth factor-beta1 (TGF-beta1) was quantified by competitive quantitative reverse transcription polymerase chain reaction using a gene specific complementary RNA standard. RESULTS In controls the gene expression of renin decreased from day 1 to day 18 and remained stable. TGF-beta1 expression increased during the first 10 days and then decreased again. Renin expression of the obstructed kidneys was reduced (p <0.05) on day 1, increased to a maximum versus controls (p <0.01) on day 10 and decreased to an unchanged elevated level (p <0.01) on days 18 and 32. Renin expression of the contralateral kidneys showed no significant alterations to control kidneys. Messenger RNA expression of TGF-beta1 of obstructed kidneys stayed decreased during the first 10 days (p <0.05), then increased excessively on day 18 (p <0.01) and slightly decreased on day 32. TGF-beta1 expression of the contralateral kidneys was parallel to controls on a slightly elevated level, increased on day 18 and returned to control level on day 32. CONCLUSIONS Within the postpartum period of nephrogenesis gene expression of renin and TGF-beta1 was decreased in obstructed kidneys compared to controls. As the renin angiotensin system and TGF-beta1 have important functions in normal kidney development, these results suggest impaired nephrogenesis of congenital obstructed kidneys even before the onset of morphological signs of hydronephrosis. These features differ from surgical induced unilateral ureteral obstruction at birth and promise new insights into the pathophysiology of congenital obstructive uropathy.

“Falsch-positive” Hodenperfusion bei Hodentorsion in der Power-Doppler-Sonographie

ZusammenfassungWir berichten über einen Patienten mit dem Bild des akuten Skrotums, bei dem die Power-Doppler-Sonographie eine erhaltene arterielle testikuläre Durchblutung zeigte. Bei therapierefraktärem Beschwerdebild erfolgte die verzögerte explorative Hodenfreilegung. Intraoperativ fand sich eine partielle Hodentorsion mit Drehung des Hodens um 180° im Bereich des Rete testis. Dieser Fall zeigt, daß der Nachweis einer arteriellen testikulären Perfusion eine Hodentorsion nicht ausschließt.SummaryWe report about a patient wich acute scrotal pain. Power Doppler sonography demonstrated arterial testicular perfusion. As no amelioration was achieved by conservative treatment, surgical exploration was done after 7 days. Intraoperatively, we found a partial testicular torsion with a 180° rotation of the testis at the rete testis. This case demonstrates, that the detection of intratesticular arterial blood flow cannot exclude testicular torsion.

In vitro investigations of new therapeutic agents on bladder tumor cell lines

In this study sensitivity of human transitional cancer cells to the anticancer agent paclitaxel, an antimicrotubular drug, and to gallium nitrate, a group IIIa metal, was compared. to that of the standard MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) drugs. The reduction of cell proliferation was evaluated after 48 h of incubation of six different cell lines with each agent using the mean transit time (MTT) assay. We investigated both monolayers and spheroids. Paclitaxel showed significantly higher growth inhibitory effects on monolayers than vinblastine, both agents targeting the antimicrotubular apparatus. This could not be reproduced on spheroids, where a survival fraction of 50% was observed even at high concentrations (10 μM). High concentrations of gallium nitrate were needed to achieve sufficient toxicity. These concentrations are beyond the concentration achievable by systemic application. Our findings suggest that paclitaxel may be a clinically useful agent for systemic and intravesical use in bladder cancer.

Clear Cell Adenocarcinoma of the Male Urethra in Association with So-Called Nephrogenic Metaplasia

A clear cell adenocarcinoma of the urethra associated with so-called nephrogenic metaplasia occurring in a 57-year-old male patient is presented. Ten months following total urethrectomy, multiple pulmonary metastases had developed. The patient died 2.5 years after surgery. The possible histogenesis of clear cell adenocarcinoma of the lower urinary tract – reported to develop in the male urethra only in a very few cases – is reviewed briefly. We favor an origin from preexisting nephrogenic metaplasia as one of the possible histogenetic pathways.

[Langerhans-cell histiocytosis of the penis].

SummaryInvolvement of the male genitalia by langerhans cell histiocytosis ist very rare. It has been reported in only three cases yet. We present a patient with recurrent disease of the skin of the penis and by proliferation involvement of the distal urethra and the corpus cavernosum. An overview of the disease and its therapy is given.ZusammenfassungDer Befall des männlichen äußeren Genitale durch die Langerhans-Zellhistiozytose ist sehr selten. Es wurde weltweit erst in 3 Fällen beschrieben. Wir berichten über einen Patienten, bei dem es im Rahmen eines rezidivierenden Krankeitsverlaufs zu einem Befall zunächst nur der Penishaut und durch Proliferation zu einer Beteiligung der Urethra und des Corpus cavernosum kam. Anhand dieser Kasuistik wird eine Übersicht über das Krankheitsbild der Langerhans-Zellhistiozytose und deren Therapie gegeben.

Comparison of Questionnaire-Based and Serological Screening for Natural Latex Allergy in Children with Neurogenic Bladder Dysfunction

Objective: We evaluated the prevalence of sensitization to natural latex in children with congenital neurogenic bladder dysfunction by patient history and serological examinations. Method: 50 consecutive children aged from 6 months to 17 years were included into the study which comprised questionnaires of patient and family histories, serological screening tests for common inhalational allergens (CAP SX1), and determination of total serum immunoglobulin E (IgE) and of latex-specific serum IgE by solid-phase immunoassays. Results: 5 children had a history of allergic reactions to natural latex; a history of atopic disposition or allergic reactions other than to latex was present in 16 children. In 10 children, latex-specific IgE levels were elevated: >0.35 kU/l; 6 out of these 10 children had no history of allergic reactions to latex. Elevated latex-specific IgE values were statistically correlated with the number of past operations (p < 0.006) and a history of atopic or allergic reactions (p < 0.0067). Clean intermittent catheterization, however, was not associated with an increased risk of latex allergy (p = 0.408). Conclusion: When screening children with congenital neurogenic bladder dysfunction for sensitization to natural latex, serological examinations of latex-specific IgE in addition to patient history may better identify patients at risk.

Magnetic resonance imaging as the primary diagnostic method for ectopic discharging ureteral insertion of a dysplastic kidney

ZusammenfassungEktop mündende Harnleiter aus dysplastischen, funktionseingeschränkten Nieren stellen ein diagnostisches Dilemma dar. Sonographie, Endoskopie oder konventionelle Röntgenuntersuchungen können häufig die Verdachtsdiagnose nicht sichern.Am Beispiel eines 6-jährigen Mädchens wird die diagnostische Aussagekraft einer wassergewichteten MR-Urographie dargestellt. Erst diese Untersuchung ermöglichte aufgrund der exakten Darstellung des ektopen Harnleiterverlaufs die zielgerichtete chirurgische Korrektur.AbstractEctopic ureters associated with dysplastic kidneys remain a diagnostic dilemma. Ultrasound, endoscopy as well as intravenous urography do not always show correct urinary tract morphology and function.We report the case of a 6-year-old girl with continuous urine dribbling to demonstrate the diagnostic value of MR urography.